Semax

1. Studied for

   BDNF and TrkB neurotrophin signaling in hippocampus and basal forebrain

   In rats, a single nose-drop application of Semax was reported to raise the level of BDNF, a protein that supports the survival and plasticity of nerve cells, in the hippocampus, along with a rise in the activation of TrkB, the receptor BDNF acts through. The reported changes were modest: BDNF protein rose at most 1.4-fold and TrkB activation 1.6-fold, with the corresponding gene messages rising about 3-fold and 2-fold. The animals given the peptide also performed more of a learned avoidance response, and the authors proposed the BDNF/TrkB system as the pathway responsible. A companion paper from the same group reported that a radioactively tagged version of the peptide bound specifically, reversibly and calcium-dependently to membranes prepared from rat basal forebrain tissue, and that BDNF protein rose in the basal forebrain three hours after application but did not rise in the cerebellum. The magnitudes matter here: these are single-digit fold changes in one brain region of a rat, not the large multiples that circulate in promotional writing. in rat studies (nose-drop application to live rats, plus a binding assay on membranes isolated from rat brain tissue) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   BDNF and TrkB neurotrophin signaling in hippocampus and basal forebrain

   In rats, a single nose-drop application of Semax was reported to raise the level of BDNF, a protein that supports the survival and plasticity of nerve cells, in the hippocampus, along with a rise in the activation of TrkB, the receptor BDNF acts through. The reported changes were modest: BDNF protein rose at most 1.4-fold and TrkB activation 1.6-fold, with the corresponding gene messages rising about 3-fold and 2-fold. The animals given the peptide also performed more of a learned avoidance response, and the authors proposed the BDNF/TrkB system as the pathway responsible. A companion paper from the same group reported that a radioactively tagged version of the peptide bound specifically, reversibly and calcium-dependently to membranes prepared from rat basal forebrain tissue, and that BDNF protein rose in the basal forebrain three hours after application but did not rise in the cerebellum. The magnitudes matter here: these are single-digit fold changes in one brain region of a rat, not the large multiples that circulate in promotional writing.^{References 1, 2}

   Modelin rat studies (nose-drop application to live rats, plus a binding assay on membranes isolated from rat brain tissue)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Brain Res. 2006;1117(1):54-60. PMID 16996037, DOI 10.1016/j.brainres.2006.07.108. And Dolotov OV, Karpenko EA, Seredenina TS, et al. J Neurochem. 2006;97 Suppl 1:82-86. PMID 16635254, DOI 10.1111/j.1471-4159.2006.03658.x.

   PubMed 16996037 PubMed 16635254

   How this citation was checked

   PubMed efetch on both PMIDs on the verification pass. 16996037 returned first author Dolotov OV, Brain Res 2006, volume 1117, issue 1, pages 54-60, DOI 10.1016/j.brainres.2006.07.108; the retrieved abstract states verbatim 'a maximal 1.4-fold increase of BDNF protein levels accompanying with 1.6-fold increase of trkB tyrosine phosporylation levels, and a 3-fold and a 2-fold increase of exon III BDNF and trkB mRNA levels, respectively, in the rat hippocampus' and, of the animals given the peptide, that they 'showed a distinct increase in the number of conditioned avoidance reactions'. 16635254 returned Dolotov OV, J Neurochem 2006, volume 97 Suppl 1, pages 82-86, DOI 10.1111/j.1471-4159.2006.03658.x; its abstract states the tritium-labelled binding was 'time dependent, specific and reversible', required calcium ions, and that BDNF rose after 3 h in basal forebrain 'but not in the cerebellum'. Both DOIs were independently re-resolved through the Crossref REST API on the same pass, returning Dolotov, Brain Research, 2006, 1117(1):54-60 and Dolotov, Journal of Neurochemistry, 2006, 97(s1):82-86 respectively. Both abstracts disclose the amount used; it is deliberately omitted here.

2. Studied for

   Cerebral ischemia models: which genes get switched on and off

   Rats given an experimental blockage of a cerebral artery were used to read out, across the whole genome, which genes change and whether the peptide changes them back. The direction of the reported effect depends on which model was used, so the two datasets should not be merged. In a model where blood flow is blocked and then restored, sequencing found 394 genes reading differently at 24 hours, with inflammation genes turned down and nerve-signaling genes turned up, the mirror image of what the blockage alone did. In a model where the blockage is permanent, a whole-genome chip study reported that the peptide mostly increased immune-system gene activity, which made up more than half of all the genes it changed at 24 hours, along with changes in blood-vessel genes. A third study reported that both Semax and its own Pro-Gly-Pro fragment increased the gene messages for growth factors and their receptors in the cortex after a permanent blockage, with Semax acting selectively in the injured cortex while the fragment's influence was mostly non-specific. This is the deepest mechanistic dataset that exists on this compound, and it is entirely in rats. in rat studies (two different surgical models: temporary artery blockage with restored blood flow, and permanent artery blockage) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Cerebral ischemia models: which genes get switched on and off

   Rats given an experimental blockage of a cerebral artery were used to read out, across the whole genome, which genes change and whether the peptide changes them back. The direction of the reported effect depends on which model was used, so the two datasets should not be merged. In a model where blood flow is blocked and then restored, sequencing found 394 genes reading differently at 24 hours, with inflammation genes turned down and nerve-signaling genes turned up, the mirror image of what the blockage alone did. In a model where the blockage is permanent, a whole-genome chip study reported that the peptide mostly increased immune-system gene activity, which made up more than half of all the genes it changed at 24 hours, along with changes in blood-vessel genes. A third study reported that both Semax and its own Pro-Gly-Pro fragment increased the gene messages for growth factors and their receptors in the cortex after a permanent blockage, with Semax acting selectively in the injured cortex while the fragment's influence was mostly non-specific. This is the deepest mechanistic dataset that exists on this compound, and it is entirely in rats.^{References 3, 4, 5}

   Modelin rat studies (two different surgical models: temporary artery blockage with restored blood flow, and permanent artery blockage)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Filippenkov IB, Stavchansky VV, Denisova AE, et al. Genes (Basel). 2020;11(6):681. PMID 32580520, DOI 10.3390/genes11060681. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. BMC Genomics. 2014;15:228. PMID 24661604, DOI 10.1186/1471-2164-15-228. Dmitrieva VG, Povarova OV, Skvortsova VI, et al. Cell Mol Neurobiol. 2010;30(1):71-79. PMID 19633950, DOI 10.1007/s10571-009-9432-0.

   PubMed 32580520 PubMed 24661604 PubMed 19633950

   How this citation was checked

   PubMed efetch on all three PMIDs on the verification pass, with all three DOIs independently re-resolved through Crossref. 32580520: Filippenkov IB, Genes (Basel) 2020, 11(6), article 681, DOI 10.3390/genes11060681; abstract states the transient MCAO model, RNA-Seq, '394 differentially expressed genes' at 24 h, and that Semax 'suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission'. 24661604: Medvedeva EV, BMC Genomics 2014, volume 15, article 228, DOI 10.1186/1471-2164-15-228; abstract states permanent MCAO, that 'the peptide predominantly enhanced the expression of genes related to the immune system', and that immune-response genes 'represented over 50% of the total number of genes' altered at 24 h. 19633950: Dmitrieva VG, Cell Mol Neurobiol 2010, 30(1):71-79, DOI 10.1007/s10571-009-9432-0; abstract states permanent MCAO and that 'Semax selectively affected the transcription of neurotrophins and their receptors in the ischemic rat cortex, whereas the influence of PGP was mainly unspecific'. Crossref returns 2009 as the online issue year for this last record and 2010 as the volume year, matching the PubMed citation. Each model designation was read off the source abstract rather than assumed.

3. Studied for

   Cerebral ischemia models: specific proteins and tissue appearance

   A rat study that measured four pre-chosen proteins after a temporary artery blockage reported that, at 24 hours, an activated form of CREB (a switch associated with repair) was higher in deeper brain structures including the damaged area, while MMP-9 and c-Fos (both associated with damage and inflammation) were lower in the neighboring cortex, and activated JNK was lower in both tissues. This study looked at four proteins picked in advance, not at the proteins of the brain as a whole. Separately, a pilot study that examined brain tissue under the microscope after a different injury, a partial whole-brain loss of blood flow, reported that both Semax and its Pro-Gly-Pro fragment increased the multiplication of support cells, blood-vessel lining cells and progenitor cells, but that only Semax reduced the visible signs of damage to nerve tissue. in rat studies (temporary artery-blockage model for the protein study; a partial whole-brain loss of blood flow for the tissue study, which its own authors call a pilot) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Cerebral ischemia models: specific proteins and tissue appearance

   A rat study that measured four pre-chosen proteins after a temporary artery blockage reported that, at 24 hours, an activated form of CREB (a switch associated with repair) was higher in deeper brain structures including the damaged area, while MMP-9 and c-Fos (both associated with damage and inflammation) were lower in the neighboring cortex, and activated JNK was lower in both tissues. This study looked at four proteins picked in advance, not at the proteins of the brain as a whole. Separately, a pilot study that examined brain tissue under the microscope after a different injury, a partial whole-brain loss of blood flow, reported that both Semax and its Pro-Gly-Pro fragment increased the multiplication of support cells, blood-vessel lining cells and progenitor cells, but that only Semax reduced the visible signs of damage to nerve tissue.^{References 6, 7}

   Modelin rat studies (temporary artery-blockage model for the protein study; a partial whole-brain loss of blood flow for the tissue study, which its own authors call a pilot)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Sudarkina OY, Filippenkov IB, Stavchansky VV, et al. Int J Mol Sci. 2021;22(12):6179. PMID 34201112, DOI 10.3390/ijms22126179. Stavchansky VV, Yuzhakov VV, Botsina AY, et al. J Mol Neurosci. 2011;45(2):177-185. PMID 20617398, DOI 10.1007/s12031-010-9421-2.

   PubMed 34201112 PubMed 20617398

   How this citation was checked

   PubMed efetch on both PMIDs on the verification pass, both DOIs independently re-resolved through Crossref. 34201112: Sudarkina OY, Int J Mol Sci 2021, 22(12), article 6179, DOI 10.3390/ijms22126179. The abstract names exactly four proteins, 'MMP-9, c-Fos, and JNK, as well as neuroprotection and recovery (CREB)', and gives the tissue-specific directions restated here, confirming this is a targeted analysis and not proteome-wide profiling. 20617398: Stavchansky VV, J Mol Neurosci 2011, 45(2):177-185, DOI 10.1007/s12031-010-9421-2; the abstract specifies 'a model of incomplete global rat brain ischemia', not MCAO, calls itself a pilot study in its title, and states 'only Semax abated the manifestation of ischemic damage to the nervous tissue'.

4. Studied for

   Cerebral ischemia models: blood vessels and cell multiplication around the injury

   In rats given a temporary artery blockage, two related peptides (Semax and a close relative) were reported, 24 hours later, to leave a higher density of nerve cells in the rim of tissue around the infarct than in rats given saline, to increase the number of dividing support cells both in that rim and in undamaged cortex, and, by staining for a blood-vessel marker, to increase both the density and the size of blood vessels in that rim. All three readouts come from one study at one timepoint. in rat studies (temporary artery-blockage model, tissue staining at 24 hours) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Cerebral ischemia models: blood vessels and cell multiplication around the injury

   In rats given a temporary artery blockage, two related peptides (Semax and a close relative) were reported, 24 hours later, to leave a higher density of nerve cells in the rim of tissue around the infarct than in rats given saline, to increase the number of dividing support cells both in that rim and in undamaged cortex, and, by staining for a blood-vessel marker, to increase both the density and the size of blood vessels in that rim. All three readouts come from one study at one timepoint.^{References 8}

   Modelin rat studies (temporary artery-blockage model, tissue staining at 24 hours)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Stavchansky VV, Yuzhakov VV, Sevan'kaeva LE, et al. Curr Issues Mol Biol. 2024;46(3):2071-2092. PMID 38534749, DOI 10.3390/cimb46030133.

   PubMed 38534749

   How this citation was checked

   PubMed efetch on the verification pass returned first author Stavchansky VV, Curr Issues Mol Biol 2024, volume 46, issue 3, pages 2071-2092, DOI 10.3390/cimb46030133, title 'Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia'. Crossref independently returned the same first author, journal, volume, issue and page range for that DOI. The abstract states the transient MCAO model, the 24-hour timepoint, the PCNA and CD31 antibodies, and each of the three outcomes as restated.

5. Studied for

   Serotonin and dopamine chemistry in the striatum

   In rodents, Semax was reported to raise a breakdown product of serotonin (5-HIAA) in the striatum, a deep brain region, by about 25 percent in tissue at two hours and by up to about 180 percent in the fluid around the cells over one to four hours, which the authors read as a positive modulating effect on the striatal serotonin system. In the same study the peptide on its own did not change dopamine or its breakdown products at all; extra dopamine release and extra movement appeared only when the peptide was given before amphetamine, which makes that a boost of the stimulant's effect rather than an effect of the peptide by itself. A second study in white rats with a chemically induced dopamine-system injury reported that the peptide reduced the severity of the resulting behavioral disturbances. A third study, using a different chemical injury model of the brain's dopamine system in rats, reported a null result for Semax: neither Semax nor Selank changed motor activity in a maze or a passive-defense test, and only Selank reduced anxiety measures. RODENT in rodent studies (the serotonin and dopamine chemistry paper says only 'in rodents' and does not name the species; the two lesion-model papers are both explicitly in rats) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Serotonin and dopamine chemistry in the striatum

   In rodents, Semax was reported to raise a breakdown product of serotonin (5-HIAA) in the striatum, a deep brain region, by about 25 percent in tissue at two hours and by up to about 180 percent in the fluid around the cells over one to four hours, which the authors read as a positive modulating effect on the striatal serotonin system. In the same study the peptide on its own did not change dopamine or its breakdown products at all; extra dopamine release and extra movement appeared only when the peptide was given before amphetamine, which makes that a boost of the stimulant's effect rather than an effect of the peptide by itself. A second study in white rats with a chemically induced dopamine-system injury reported that the peptide reduced the severity of the resulting behavioral disturbances. A third study, using a different chemical injury model of the brain's dopamine system in rats, reported a null result for Semax: neither Semax nor Selank changed motor activity in a maze or a passive-defense test, and only Selank reduced anxiety measures.^{References 9, 10, 11}

   Modelin rodent studies (the serotonin and dopamine chemistry paper says only 'in rodents' and does not name the species; the two lesion-model papers are both explicitly in rats)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Eremin KO, Kudrin VS, Saransaari P, et al. Neurochem Res. 2005;30(12):1493-1500. PMID 16362768, DOI 10.1007/s11064-005-8826-8. Levitskaya NG, Sebentsova EA, Andreeva LA, et al. Neurosci Behav Physiol. 2004;34(4):399-405. PMID 15341218, DOI 10.1023/b:neab.0000018752.59465.28. Slominsky PA, Shadrina MI, Kolomin TA, et al. Dokl Biol Sci. 2017;474(1):106-109. PMID 28702721, DOI 10.1134/S0012496617030048.

   PubMed 16362768 PubMed 15341218 PubMed 28702721

   How this citation was checked

   PubMed efetch on all three PMIDs on the verification pass, all three DOIs independently re-resolved through Crossref. 16362768: Eremin KO, Neurochem Res 2005, 30(12):1493-1500; the abstract states verbatim 'This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites' and supplies the +25 percent tissue and 180 percent extracellular 5-HIAA figures. Critically, that abstract describes its subjects only as 'rodents' and never names a species, which is why the model field here says the species is not specified rather than claiming mice. 15341218: Levitskaya NG, Neurosci Behav Physiol 2004, 34(4):399-405; its abstract explicitly says 'white rats' and supports the lesion-model sentence. 28702721: Slominsky PA, Dokl Biol Sci 2017, 474(1):106-109; its abstract explicitly says rats and states 'both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals' while 'Selank decreased level of anxiety'. Two of the three abstracts disclose amounts; they are deliberately omitted here.

6. Studied for

   Copper binding and the chemistry of the amyloid-beta protein

   Test-tube and cell work reported that Semax forms a stable complex with copper, prevents the amyloid-beta protein from forming its own complex with copper, and shows anti-clumping and protective properties particularly when copper is present, with the authors proposing that it blocks fiber formation by interfering with the copper-bound form of the protein. A follow-up reported that the peptide can strip copper away from copper-loaded amyloid-beta, change how that complex cycles electrons, lower the reactive oxygen species it generates, and protect a human nerve-like cell line from the resulting oxidative stress. This is chemistry and cell-dish work. It is not evidence about any condition in a person. in test tubes and cultured cells (fluorescence and calorimetry assays, artificial membrane models, and viability assays in SH-SY5Y cells, a human neuroblastoma cell line) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Copper binding and the chemistry of the amyloid-beta protein

   Test-tube and cell work reported that Semax forms a stable complex with copper, prevents the amyloid-beta protein from forming its own complex with copper, and shows anti-clumping and protective properties particularly when copper is present, with the authors proposing that it blocks fiber formation by interfering with the copper-bound form of the protein. A follow-up reported that the peptide can strip copper away from copper-loaded amyloid-beta, change how that complex cycles electrons, lower the reactive oxygen species it generates, and protect a human nerve-like cell line from the resulting oxidative stress. This is chemistry and cell-dish work. It is not evidence about any condition in a person.^{References 12, 13}

   Modelin test tubes and cultured cells (fluorescence and calorimetry assays, artificial membrane models, and viability assays in SH-SY5Y cells, a human neuroblastoma cell line)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Sciacca MFM, Naletova I, Giuffrida ML, Attanasio F. ACS Chem Neurosci. 2022;13(4):486-496. PMID 35080861, DOI 10.1021/acschemneuro.1c00707. Tomasello MF, Di Rosa MC, Naletova I, et al. Bioinorg Chem Appl. 2025;2025:4226220. PMID 40496623, DOI 10.1155/bca/4226220.

   PubMed 35080861 PubMed 40496623

   How this citation was checked

   PubMed efetch on both PMIDs on the verification pass, with both DOIs re-extracted specifically from the PubmedData ArticleIdList (a naive parse of the record returns reference DOIs instead) and then independently re-resolved through Crossref. 35080861: Sciacca MFM, ACS Chem Neurosci 2022, 13(4):486-496, DOI 10.1021/acschemneuro.1c00707, title 'Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models'; the abstract names the spectrofluorometric, calorimetric and MTT methods and states that Semax 'is able to prevent the formation of Abeta:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+'. 40496623: Tomasello MF, Bioinorg Chem Appl 2025, volume 2025, article 4226220, DOI 10.1155/bca/4226220; the abstract states the study was done in vitro, names SH-SY5Y cells, and states the metal-stripping, redox-cycling and ROS-lowering results as restated.

7. Studied for

   Acute and chronic stress models

   Two rat studies looked at the peptide under stress. In an acute restraint stress study, giving Semax or a close relative before the stressor was reported to blunt the behavioral changes the stressor caused, and sequencing of the hippocampus four and a half hours later reported that both peptides tended to push gene activity back in the opposite direction from the way the stressor had pushed it. In a chronic unpredictable stress study, Semax and Melanotan II were each given as separate study arms, and sustained application across the stress period was reported to reverse or substantially blunt four consequences of the stress: loss of preference for sugar water (a standard read on loss of pleasure), suppressed body-weight gain, adrenal gland enlargement, and lower hippocampal BDNF. That same study reported a null result on a fifth measure: neither the stress procedure nor the peptides changed how long the rats stayed immobile in a forced swim test. in rat studies (male rats; an acute restraint stress model and a chronic unpredictable stress model) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Acute and chronic stress models

   Two rat studies looked at the peptide under stress. In an acute restraint stress study, giving Semax or a close relative before the stressor was reported to blunt the behavioral changes the stressor caused, and sequencing of the hippocampus four and a half hours later reported that both peptides tended to push gene activity back in the opposite direction from the way the stressor had pushed it. In a chronic unpredictable stress study, Semax and Melanotan II were each given as separate study arms, and sustained application across the stress period was reported to reverse or substantially blunt four consequences of the stress: loss of preference for sugar water (a standard read on loss of pleasure), suppressed body-weight gain, adrenal gland enlargement, and lower hippocampal BDNF. That same study reported a null result on a fifth measure: neither the stress procedure nor the peptides changed how long the rats stayed immobile in a forced swim test.^{References 14, 15}

   Modelin rat studies (male rats; an acute restraint stress model and a chronic unpredictable stress model)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Filippenkov IB, Stavchansky VV, Glazova NY, et al. Int J Mol Sci. 2021;22(18):10054. PMID 34576218, DOI 10.3390/ijms221810054. Inozemtseva LS, Yatsenko KA, Glazova NY, et al. Eur J Pharmacol. 2024;984:177068. PMID 39442746, DOI 10.1016/j.ejphar.2024.177068.

   PubMed 34576218 PubMed 39442746

   How this citation was checked

   PubMed efetch on both PMIDs on the verification pass, with both DOIs independently re-resolved through Crossref. 34576218: Filippenkov IB, Int J Mol Sci 2021, 22(18), article 10054, DOI 10.3390/ijms221810054; the abstract states application 30 minutes before acute restraint stress 'attenuated ARS-induced behavioral alterations', samples collected 4.5 h after the stressor, and that 'both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa'. 39442746: Inozemtseva LS, Eur J Pharmacol 2024, volume 984, article 177068, DOI 10.1016/j.ejphar.2024.177068; the abstract states male Sprague-Dawley rats and daily saline, Semax or MTII arms run separately, which is why Melanotan II is named here rather than the result being attributed to Semax alone, that the peptides 'reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF', and that 'In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected'. Both abstracts disclose amounts; they are deliberately omitted here.

8. Studied for

   Human study: recovery after a loss of blood flow in the brain, and a blood growth-factor marker

   In a study of 110 people in rehabilitation after a loss of blood flow in the brain (43 men and 67 women, average age 58), participants were split into an early rehabilitation group and a late rehabilitation group, and each of those was split again into those who received semax and those who did not. Semax was associated with higher BDNF in the blood that stayed elevated for the whole study period, and with faster improvement and a better final score on the Barthel index, a standard measure of independence in daily activities. The authors reported a positive correlation between blood BDNF and Barthel score, and separately a correlation between early rehabilitation and improvement in motor performance; the paper's own conclusion attributes faster functional recovery and improved motor performance to early rehabilitation and semax together. The published abstract does not describe randomization or blinding, and outcomes were compared between semax and non-semax subgroups within the rehabilitation-timing groups, so the design does not support a causal reading. in a human study (110 people; how participants were assigned and whether anyone was blinded is not described in the published abstract) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Human study: recovery after a loss of blood flow in the brain, and a blood growth-factor marker

   In a study of 110 people in rehabilitation after a loss of blood flow in the brain (43 men and 67 women, average age 58), participants were split into an early rehabilitation group and a late rehabilitation group, and each of those was split again into those who received semax and those who did not. Semax was associated with higher BDNF in the blood that stayed elevated for the whole study period, and with faster improvement and a better final score on the Barthel index, a standard measure of independence in daily activities. The authors reported a positive correlation between blood BDNF and Barthel score, and separately a correlation between early rehabilitation and improvement in motor performance; the paper's own conclusion attributes faster functional recovery and improved motor performance to early rehabilitation and semax together. The published abstract does not describe randomization or blinding, and outcomes were compared between semax and non-semax subgroups within the rehabilitation-timing groups, so the design does not support a causal reading.^{References 16}

   Modelin a human study (110 people; how participants were assigned and whether anyone was blinded is not described in the published abstract)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(3 Vyp 2):61-68. PMID 29798983, DOI 10.17116/jnevro20181183261-68.

   PubMed 29798983

   How this citation was checked

   PubMed efetch on the verification pass returned all five named authors in that order, Zh Nevrol Psikhiatr Im S S Korsakova 2018, volume 118, issue '3. Vyp. 2', pages 61-68, DOI 10.17116/jnevro20181183261-68; Crossref independently resolved that DOI to Gusev, Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova, 2018, volume 118, first page 61. The structured abstract supplies n=110, the 43 men and 67 women split, the mean age of 58.0, and both rehabilitation-timing windows verbatim. The RESULTS section states 'a correlation between early rehabilitation and motor performance improvement', and the CONCLUSION section states verbatim 'Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance'; both are restated here, and a prior draft's contrast clause claiming that motor improvement tracked rehabilitation 'rather than' the peptide has been deleted because the paper does not say that. The abstract contains no statement of randomization or blinding, so neither is asserted, and it discloses a regimen that is deliberately omitted here.

9. Studied for

   Human study: how brain regions communicate at rest

   Fifty-two healthy volunteers were scanned three times in an MRI at rest, once before and then 5 and 20 minutes after receiving Semax, Selank, or placebo, with regions of interest chosen in advance including the amygdala and the dorsolateral prefrontal cortex on both sides. The authors reported differences, both between groups and between timepoints, in how strongly the right amygdala was coupled to a right-hemisphere region spanning several temporal-lobe structures, and described both shared and compound-specific effects of the two peptides. This measured coupling between brain regions. It did not measure task performance, mood, cognition, or any clinical outcome, and no benefit to any participant was reported. Randomization and blinding are not described in the abstract. in a human study (52 healthy volunteers, resting-state MRI, with a placebo arm) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Human study: how brain regions communicate at rest

   Fifty-two healthy volunteers were scanned three times in an MRI at rest, once before and then 5 and 20 minutes after receiving Semax, Selank, or placebo, with regions of interest chosen in advance including the amygdala and the dorsolateral prefrontal cortex on both sides. The authors reported differences, both between groups and between timepoints, in how strongly the right amygdala was coupled to a right-hemisphere region spanning several temporal-lobe structures, and described both shared and compound-specific effects of the two peptides. This measured coupling between brain regions. It did not measure task performance, mood, cognition, or any clinical outcome, and no benefit to any participant was reported. Randomization and blinding are not described in the abstract.^{References 17}

   Modelin a human study (52 healthy volunteers, resting-state MRI, with a placebo arm)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Panikratova YR, Lebedeva IS, Sokolov OY, et al. Dokl Biol Sci. 2020;490(1):9-11. PMID 32342318, DOI 10.1134/S001249662001007X.

   PubMed 32342318

   How this citation was checked

   PubMed efetch on the verification pass returned first author Panikratova YR with Lebedeva IS and Sokolov OY as the next two authors, Dokl Biol Sci 2020, volume 490, issue 1, pages 9-11, DOI 10.1134/S001249662001007X, title 'Functional Connectomic Approach to Studying Selank and Semax Effects'. Crossref independently returned Panikratova, Doklady Biological Sciences, 2020, 490(1):9-11 for that DOI. The abstract supplies the 52 healthy participants, the three-timepoint design, the placebo arm, the amygdala and DLPFC regions of interest, and the specific finding 'between the right amygdala and a region in fusiform, inferior and middle temporal as well as parahippocampal gyri in the right hemisphere', so the anatomy restated here is quoted rather than loosely characterized.

10. Studied for

    How much reaches the brain after nose-drop application

    Using a version of the peptide tagged with radioactive tritium, researchers tracked how it entered the brain and blood of rats after nose-drop application. They reported that 0.093 percent of the total radioactivity introduced was present per gram of rat brain two minutes afterward, of which about 80 percent was still intact peptide and the rest was breakdown products, and that the peptide is broken down quickly, with 'the tripeptide Pro-Gly-Pro prevailing in biological samples'. That last point is why researchers study Pro-Gly-Pro as an active fragment in its own right. The fraction reaching the brain is small, and this was measured in rats, not people. in rat studies (radioactively tagged peptide, nose-drop application) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    How much reaches the brain after nose-drop application

    Using a version of the peptide tagged with radioactive tritium, researchers tracked how it entered the brain and blood of rats after nose-drop application. They reported that 0.093 percent of the total radioactivity introduced was present per gram of rat brain two minutes afterward, of which about 80 percent was still intact peptide and the rest was breakdown products, and that the peptide is broken down quickly, with 'the tripeptide Pro-Gly-Pro prevailing in biological samples'. That last point is why researchers study Pro-Gly-Pro as an active fragment in its own right. The fraction reaching the brain is small, and this was measured in rats, not people.^{References 18}

    Modelin rat studies (radioactively tagged peptide, nose-drop application)

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Shevchenko KV, Nagaev IIu, Alfeeva LIu, et al. Bioorg Khim. 2006;32(1):64-70. PMID 16523722. English translation: Russ J Bioorg Chem. 2006;32(1):57-62, DOI 10.1134/s1068162006010055.

    PubMed 16523722

    How this citation was checked

    PubMed efetch on the verification pass returned first author Shevchenko KV, Bioorg Khim 2006, volume 32, issue 1, pages 64-70. The abstract supplies the 0.093 percent per gram figure, the two-minute timepoint, the 80 percent intact fraction, and the statement that 'the tripeptide Pro-Gly-Pro prevailing in biological samples'. Crossref resolves the DOI 10.1134/s1068162006010055 to the English translation, Russian Journal of Bioorganic Chemistry 2006, volume 32, issue 1, pages 57-62, first author Shevchenko, so the DOI is attached to the translation line rather than to the Russian original, whose pagination differs; a prior draft merged the Russian pagination with the translation's DOI in a single citation string, which misstated the record. The abstract discloses the amount used; it is deliberately omitted here.

11. Studied for

    Neurotrophin gene switching in cultured support cells

    In glial cells (the brain's support cells) taken from newborn rats and grown in a dish, adding Semax was reported to raise the gene messages for two growth factors, NGF and BDNF. The largest change was at 30 minutes, when the BDNF message was about eight times control and the NGF message about five times control. This is a change in gene messages in isolated cells in a dish; it does not show that anything happens in a living animal, and it says nothing about protein levels. in cultured cells (glial cells taken from the basal forebrain of newborn rats) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Neurotrophin gene switching in cultured support cells

    In glial cells (the brain's support cells) taken from newborn rats and grown in a dish, adding Semax was reported to raise the gene messages for two growth factors, NGF and BDNF. The largest change was at 30 minutes, when the BDNF message was about eight times control and the NGF message about five times control. This is a change in gene messages in isolated cells in a dish; it does not show that anything happens in a living animal, and it says nothing about protein levels.^{References 19}

    Modelin cultured cells (glial cells taken from the basal forebrain of newborn rats)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Shadrina MI, Dolotov OV, Grivennikov IA, et al. Neurosci Lett. 2001;308(2):115-118. PMID 11457573, DOI 10.1016/s0304-3940(01)01994-2.

    PubMed 11457573

    How this citation was checked

    PubMed efetch on the verification pass returned first author Shadrina MI, Neurosci Lett 2001, volume 308, issue 2, pages 115-118, DOI 10.1016/s0304-3940(01)01994-2, title 'Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog'. The retrieved abstract states the cells were glial cells from the basal forebrain of newborn rats and gives the eight-fold BDNF and five-fold NGF mRNA figures at 30 minutes verbatim. The DOI was independently re-resolved through Crossref on the same pass, returning Shadrina, Neuroscience Letters, 2001, 308(2):115-118.

12. Studied for

    A damaging chemical surge after loss of blood flow

    In rats subjected to a partial whole-brain loss of blood flow, nitric oxide and markers of fat damage in tissue both went up. Semax was reported to be effective at blunting the nitric oxide rise and at restoring neurological function, whereas glycine, the comparison substance in the same study, did neither. Stated as blunting rather than preventing, which is the wording of the paper's own abstract even though its title uses the stronger word. in rat studies (partial whole-brain loss of blood flow) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    A damaging chemical surge after loss of blood flow

    In rats subjected to a partial whole-brain loss of blood flow, nitric oxide and markers of fat damage in tissue both went up. Semax was reported to be effective at blunting the nitric oxide rise and at restoring neurological function, whereas glycine, the comparison substance in the same study, did neither. Stated as blunting rather than preventing, which is the wording of the paper's own abstract even though its title uses the stronger word.^{References 20}

    Modelin rat studies (partial whole-brain loss of blood flow)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Bashkatova VG, Koshelev VB, Fadyukova OE, et al. Brain Res. 2001;894(1):145-149. PMID 11245825, DOI 10.1016/s0006-8993(00)03324-2.

    PubMed 11245825

    How this citation was checked

    PubMed efetch on the verification pass returned first author Bashkatova VG, Brain Res 2001, volume 894, issue 1, pages 145-149, DOI 10.1016/s0006-8993(00)03324-2, and Crossref independently returned Bashkatova, Brain Research, 2001, 894(1):145-149 for the same DOI. The retrieved abstract reads 'While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning', which is the basis for using 'abating' here even though the article title says 'prevents'.

13. Studied for

    Nerve cell calcium handling under chemical stress

    In rat cerebellar nerve cells grown in a dish and then poisoned with glutamate, Semax and its Pro-Gly-Pro fragment were reported to delay the point at which the cells lose control of their internal calcium and their mitochondria lose voltage, and to improve cell survival by about 30 percent on average. The concentrations used in the dish were in the high micromolar range, far above anything measured in a living animal, which is a real limit on how much the result means. A separate 2025 study in slices of rat brain reported that applying the peptide increased the frequency of spontaneous calcium fluctuations in pyramidal cells of the hippocampal CA1 region, but had no significant effect on an acid-triggered calcium rise in cerebellar granule cells, from which those authors concluded that the peptide's protective effect is probably not explained by blocking that acid-sensing calcium route. in cultured cells (rat cerebellar granule cells in a dish) for the glutamate study, and in slices of rat brain kept alive outside the animal for the 2025 calcium study Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Nerve cell calcium handling under chemical stress

    In rat cerebellar nerve cells grown in a dish and then poisoned with glutamate, Semax and its Pro-Gly-Pro fragment were reported to delay the point at which the cells lose control of their internal calcium and their mitochondria lose voltage, and to improve cell survival by about 30 percent on average. The concentrations used in the dish were in the high micromolar range, far above anything measured in a living animal, which is a real limit on how much the result means. A separate 2025 study in slices of rat brain reported that applying the peptide increased the frequency of spontaneous calcium fluctuations in pyramidal cells of the hippocampal CA1 region, but had no significant effect on an acid-triggered calcium rise in cerebellar granule cells, from which those authors concluded that the peptide's protective effect is probably not explained by blocking that acid-sensing calcium route.^{References 21, 22}

    Modelin cultured cells (rat cerebellar granule cells in a dish) for the glutamate study, and in slices of rat brain kept alive outside the animal for the 2025 calcium study

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Storozhevykh TP, Tukhbatova GR, Senilova YE, et al. Bull Exp Biol Med. 2007;143(5):601-604. PMID 18239779, DOI 10.1007/s10517-007-0192-x. Kolbaev SN, Sharonova IN, Skrebitsky VG. Bull Exp Biol Med. 2025;179(4):416-420. PMID 41171324, DOI 10.1007/s10517-025-06501-z.

    PubMed 18239779 PubMed 41171324

    How this citation was checked

    PubMed efetch on the verification pass for 18239779 returned Storozhevykh TP, Bull Exp Biol Med 2007, 143(5):601-604, DOI 10.1007/s10517-007-0192-x, with Crossref independently confirming the same author, journal, volume, issue and pages; the abstract gives the micromolar concentrations and the roughly 30 percent survival improvement verbatim. The 2025 report was newly located as a PubMed record on that pass (a prior pass had it as Crossref-only): a PubMed esearch on its DOI returned exactly one record, PMID 41171324, and efetch on that PMID returned Kolbaev SN, Sharonova IN, Skrebitsky VG, Bull Exp Biol Med 2025, volume 179, issue 4, pages 416-420, DOI 10.1007/s10517-025-06501-z, title 'The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons'. Crossref independently returned the same three authors, journal, volume, issue and page range. The retrieved abstract states the hippocampal-slice and cerebellar-slice preparations, the increase in spontaneous fluctuation frequency 'in the pyramidal layer cells of the hippocampal CA1 field', the null result on 'proton-stimulated increase in [Ca2+]i in cerebellar granule cells', and the authors' own conclusion about acid-sensing ion channels, so every element restated here comes from the abstract rather than from the title.

14. Studied for

    A mouse line bred to deposit amyloid in the brain

    In mice genetically engineered to deposit amyloid in the brain, Semax and a chemical derivative of it were tested on a set of behavioral tests (open field, novel object recognition, and Barnes maze), which the authors read as showing improved cognitive function in the mice. Examination of brain tissue reported that both peptides reduced the number of amyloid clumps in the cortex and hippocampus. This is one preclinical study. It extends the copper and amyloid test-tube chemistry into a live animal, and it is not clinical evidence. in mouse studies (APPswe/PS1dE9/Blg transgenic mice, a line bred to deposit amyloid) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    A mouse line bred to deposit amyloid in the brain

    In mice genetically engineered to deposit amyloid in the brain, Semax and a chemical derivative of it were tested on a set of behavioral tests (open field, novel object recognition, and Barnes maze), which the authors read as showing improved cognitive function in the mice. Examination of brain tissue reported that both peptides reduced the number of amyloid clumps in the cortex and hippocampus. This is one preclinical study. It extends the copper and amyloid test-tube chemistry into a live animal, and it is not clinical evidence.^{References 23}

    Modelin mouse studies (APPswe/PS1dE9/Blg transgenic mice, a line bred to deposit amyloid)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Radchenko AI, Kuzubova EV, Apostol AA, et al. Acta Naturae. 2025;17(4):110-120. PMID 41479572, DOI 10.32607/actanaturae.27808.

    PubMed 41479572

    How this citation was checked

    PubMed efetch on the verification pass returned first author Radchenko AI, Acta Naturae 2025, volume 17, issue 4, pages 110-120, DOI 10.32607/actanaturae.27808, title 'The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease'. That title is reproduced verbatim because altering a published title would falsify the record; it is the one place a disease is named anywhere in this file. Crossref independently returned Radchenko, Acta Naturae, 2025, 17(4):110-120 for that DOI. The abstract names the APPswe/PS1dE9/Blg strain and reads verbatim 'The open field, novel object recognition, and Barnes maze tests demonstrated that both Semax and its derivative improved cognitive functions in mice', which is why this entry attributes the cognitive reading to the authors rather than claiming that each of the three named tests individually measured cognition; the open field test is primarily a locomotor and anxiety assay. The abstract also states the reduction in amyloid inclusions in cortex and hippocampus.

15. Studied for

    Early-life drug exposure model

    White rat pups were given the drug fluvoxamine in their first two weeks of life, an exposure the study reports produces long-lasting changes in anxiety-related behavior, learning, and brain messenger chemicals. Semax given over the following two weeks was reported to reduce the anxiety-like behavior, improve the learning measures, and normalize the brain chemical levels that the exposure had altered. This is one preclinical study in one specific developmental-injury model. in rat studies (white rats, a newborn-exposure paradigm) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Early-life drug exposure model

    White rat pups were given the drug fluvoxamine in their first two weeks of life, an exposure the study reports produces long-lasting changes in anxiety-related behavior, learning, and brain messenger chemicals. Semax given over the following two weeks was reported to reduce the anxiety-like behavior, improve the learning measures, and normalize the brain chemical levels that the exposure had altered. This is one preclinical study in one specific developmental-injury model.^{References 24}

    Modelin rat studies (white rats, a newborn-exposure paradigm)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Glazova NY, Manchenko DM, Volodina MA, et al. Neuropeptides. 2021;86:102114. PMID 33418449, DOI 10.1016/j.npep.2020.102114.

    PubMed 33418449

    How this citation was checked

    PubMed efetch on the verification pass returned first author Glazova NY, Neuropeptides 2021, volume 86, article 102114, DOI 10.1016/j.npep.2020.102114, title 'Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats'. Crossref independently returned Glazova, Neuropeptides, 2021, volume 86, article 102114 for that DOI. The abstract supplies the white-rat species, the postnatal day 1-14 exposure window and the day 15-28 application window, and states 'Semax administration reduced the anxiety-like behaviour, improved learning abilities and normalized the levels of brain biogenic amines impaired by the FA exposure'.

16. Studied for

    Inhibition of peptide-degrading enzymes in serum

    In an assay using human serum, Semax and Selank were each reported to slow the enzymes that break down enkephalins, the body's own opioid-like signaling peptides, with Semax the more potent of the two and both described as more potent than several standard peptidase inhibitors tested alongside. Structure work in the same paper reported that the five-amino-acid fragments of both peptides also inhibited, while the three-, four- and six-amino-acid fragments did not. The authors proposed this as one possible mechanism behind the peptides' activity. This is an enzyme measurement in a tube of serum. It is not a pain measurement, an analgesia result, or an observation in any living organism. in a test-tube assay (enzymes in human serum) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Inhibition of peptide-degrading enzymes in serum

    In an assay using human serum, Semax and Selank were each reported to slow the enzymes that break down enkephalins, the body's own opioid-like signaling peptides, with Semax the more potent of the two and both described as more potent than several standard peptidase inhibitors tested alongside. Structure work in the same paper reported that the five-amino-acid fragments of both peptides also inhibited, while the three-, four- and six-amino-acid fragments did not. The authors proposed this as one possible mechanism behind the peptides' activity. This is an enzyme measurement in a tube of serum. It is not a pain measurement, an analgesia result, or an observation in any living organism.^{References 25}

    Modelin a test-tube assay (enzymes in human serum)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Kost NV, Sokolov OY, Gabaeva MV, Grivennikov IA, Andreeva LA, Myasoedov NF, Zozulya AA. Bioorg Khim. 2001;27(3):180-183. PMID 11443939. English translation: Russ J Bioorg Chem. 2001;27(3):156-159, DOI 10.1023/a:1011373002885.

    PubMed 11443939

    How this citation was checked

    PubMed efetch on the verification pass returned all seven named authors in that order (transliterated in PubMed as Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA), Bioorg Khim 2001, volume 27, issue 3, pages 180-183, title 'Semax and selank inhibit the enkephalin-degrading enzymes from human serum'. The abstract states verbatim that the inhibitory effects 'are more pronounced than those of puromycin, bacitracin, and some other inhibitors of peptidases' and that 'their pentapeptide fragments also possessed an inhibitory effect; tri-, tetra-, and hexapeptide fragments did not display such an effect'. Crossref resolves the DOI to the English translation, Russian Journal of Bioorganic Chemistry, volume 27, issue 3, pages 156-159, first author Kost, which is why the DOI is attached to the translation line here rather than to the Russian-language original: the two records have different pagination and merging them would misstate the citation. The abstract discloses potency constants for the enzyme assay; those are potency measurements in a tube rather than amounts given to anything, and they are not restated here.

17. Studied for

    Inflammation signals after spinal cord injury

    In male rats given an acute spinal cord injury by clamping the cord after surgery, with a lighter clamp for mild injury and a heavier one for severe injury, the peptide was given by nose drops and compared against saline for the levels of three calming immune signals, measured by tissue staining at 3 and 6 hours. In the mildly injured animals the peptide group showed higher calming-signal levels at 3 hours, but only two of the three (IL-10 and IL-13) were significantly raised at 6 hours. In the severely injured animals the peptide group showed higher IL-10 and IL-13 at 3 hours and higher IL-4 and IL-10 at 6 hours. The results differ by injury severity and by timepoint and should not be flattened into a blanket increase in all three signals. One study, a very short observation window of six hours, and the authors themselves state that further research is needed. Venue caveat: this appeared in F1000Research, a platform that publishes first and conducts open peer review afterward, rather than a conventionally pre-reviewed journal, so it carries less editorial filtering than the other citations here. in rat studies (male Sprague Dawley rats, acute spinal cord injury by clamp compression) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Inflammation signals after spinal cord injury

    In male rats given an acute spinal cord injury by clamping the cord after surgery, with a lighter clamp for mild injury and a heavier one for severe injury, the peptide was given by nose drops and compared against saline for the levels of three calming immune signals, measured by tissue staining at 3 and 6 hours. In the mildly injured animals the peptide group showed higher calming-signal levels at 3 hours, but only two of the three (IL-10 and IL-13) were significantly raised at 6 hours. In the severely injured animals the peptide group showed higher IL-10 and IL-13 at 3 hours and higher IL-4 and IL-10 at 6 hours. The results differ by injury severity and by timepoint and should not be flattened into a blanket increase in all three signals. One study, a very short observation window of six hours, and the authors themselves state that further research is needed. Venue caveat: this appeared in F1000Research, a platform that publishes first and conducts open peer review afterward, rather than a conventionally pre-reviewed journal, so it carries less editorial filtering than the other citations here.^{References 26}

    Modelin rat studies (male Sprague Dawley rats, acute spinal cord injury by clamp compression)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Asadullah A, Bajamal AH, Parenrengi MA, et al. F1000Res. 2023;12:194 (version 2). PMID 41179234, DOI 10.12688/f1000research.127413.2.

    PubMed 41179234

    How this citation was checked

    PubMed efetch on the verification pass returned first author Asadullah A, F1000Res 2023, volume 12, page 194, DOI 10.12688/f1000research.127413.2, which is the version-2 DOI; Crossref independently resolved that same DOI to Asadullah, F1000Research, volume 12, article 194, with the version-2 deposit dated 2025, which is why the version is named explicitly in the citation. The retrieved structured abstract supplies the laminectomy at the second thoracic vertebra, the two clip weights for mild and severe injury, intranasal application versus 0.9 percent NaCl placebo, immunohistochemistry, the 3-hour and 6-hour termination points, and the severity-stratified and timepoint-stratified results exactly as restated, including 'only IL-10 and IL-13 were elevated significantly at 6 hours' in the mild-injury group. The clip weights are a description of the surgical injury model, not an amount of anything given.

10 moderate / 7 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.