Investigation of the Effects of Agomelatine in Rats with Experimental Cerebral Ischemia/Reperfusion Model

English (OpenAlex)

Objective: The present study aimed to investigate the neuroprotective effects of agomelatine in a rat model of cerebral ischemia/reperfusion injury, a major pathological event underlying ischemic stroke. Methods: Male Sprague Dawley rats included in the study were divided into four groups (n = 10/group): sham, CI/R, CI/R + 20 mg/kg Agm and CI/R + 40 mg/kg Agm. Sixty minutes of ischemia was induced in all groups except the sham group. One hour after ischemia, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, while 20 and 40 mg/kg agomelatine was administered to CI/R + Agm groups. During the three-day reperfusion period, the rats underwent neurological deficit score (NDS), rotarod, adhesive removal, and grip strength tests. At the end of the experiment, animals were decapitated and brain tissues were collected. In the collected brain tissues, infarct area was determined by TTC staining, and levels of apoptosis (Bcl-2, Bax) and autophagy (Beclin-1, ATG5, ATG7, p62) proteins were determined by Western blot. Statistical analysis of the obtained data was performed. Results: Compared with the CI/R group, agomelatine-treated groups showed significantly lower NDSs and adhesive removal times, as well as higher rotarod retention times and grip strength values (p < 0.05). Infarct area was significantly reduced following agomelatine treatment (p < 0.05). Agomelatine increased Bcl-2, Beclin-1, ATG5, and ATG7 protein levels while decreasing Bax and p62 expression compared with the CI/R group (p < 0.05). Conclusions: Agomelatine attenuated neurological deficits and infarct formation following CI/R injury. These neuroprotective effects may be associated with suppression of apoptosis and enhancement of autophagy-related pathways.