Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.

Preclinical animal study investigating the molecular mechanisms of Semax in a rat model of transient middle cerebral artery occlusion (tMCAO).

“Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke.”

Semax treatment downregulated active JNK (pJNK) in both subcortical structures and the frontoparietal cortex.

“The total content of pJNK was increased by more than two-fold in the subcortex (Figure 2a) and cerebral cortex (Figure 2b) of the IR relative to the SH group; in turn, these levels were decreased by more than 1.5-fold after treatment with Semax.”

Semax treatment upregulated active CREB (pCREB) in subcortical structures, whereas ischemia alone had decreased its levels.

“The level of pCREB was decreased by more than 1.4-fold in the subcortex during ischemia, whereas Semax increased its levels by more than 1.5-fold (Figure 2c).”

The study analyzed the expression of only four specific proteins, which may not fully capture the proteomic response to Semax.

“A limitation of our study is the analysis of the expression of only four proteins; the genome-wide proteomic analysis may reveal some additional proteins involved in the response to Semax administration during ischemia.”