Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia

Neurotrophic factors like BDNF are essential for brain repair after injury, and finding ways to boost their production during the critical window after stroke could save lives and cognitive function. This study by Dmitrieva, Povarova, Skvortsova, and colleagues, published in Cell and Molecular Neurobiology, examined how Semax activates neurotrophin gene expression after cerebral ischemia.

The researchers induced focal cerebral ischemia in rats and administered either Semax or its component tripeptide Pro-Gly-Pro (PGP) during the acute phase. They measured the transcription of neurotrophin genes and their receptors at multiple time points — 3, 24, and 72 hours after the ischemic event — to track the temporal dynamics of the neuroprotective response.

The findings revealed a precisely orchestrated response. Semax enhanced transcription of BDNF, TrkC, and TrkA at 3 hours post-ischemia, while later time points showed increased NT-3 and NGF expression. Critically, Semax selectively affected neurotrophin transcription in the ischemic rat cortex, whereas PGP's influence was mainly nonspecific. This selectivity suggests Semax has more targeted therapeutic potential for acute stroke treatment.

This study provides crucial mechanistic evidence for Semax's neuroprotective effects. By showing that the peptide rapidly and selectively activates the brain's own neurotrophic repair systems, it supports Semax's use in acute neuroprotective protocols. The temporal dynamics — early BDNF activation followed by sustained NGF and NT-3 expression — suggest Semax supports both immediate brain protection and longer-term neural repair.