Semax-Induced Changes in Growth Factor mRNA Levels in the Rat Brain on the Third Day After Ischemia

The peptide Semax effectively protects brain tissues against ischemic stroke. However, the molecular mechanisms that underlie its action remain unknown. We used the focal cerebral ischemia rat model with permanent middle cerebral artery occlusion (pMCAO). During the experiments, animals were given intraperitoneal injections of Semax, Pro-Gly-Pro, or saline. We studied the effect of the peptides on the expression of more than 80 growth factor genes in the cortex. As a response to Semax administration, alterations in the expression of growth factor genes were detected at 3, 24, and 72 h after pMCAO. The most pronounced effects of Semax, i.e., the downregulation of the transcripts of 20 genes and the upregulation of 12 growth factor genes, were observed 3 days after artery occlusion. According to our data, Semax promoted the upregulation (by ≥10-fold) of the Csf3 and Artn genes, as well as of the cytokine genes Il1b and Il6. The peptide products of these genes have regulatory properties and exert neuroprotective effects in injured brain tissues. We presume that Semax triggers neuroprotective mechanisms by affecting these systems via the regulation of the expression of growth factor genes.