Investigation of the effects of Agomelatin on experimental cerebral ischemia/reperfusion modeled rats

Aim: In this study aimed to investigate the effects of Agomelatine, which plays a role in melatonergic and serotonergic system activity and is known to support neurogenesis, on the Cerebral Ischemia (CI)/Reperfusion (R) process, which causes intense damage to neurons. Materials and Methods Sprague Dawley male rats included in the study were divided into four groups (n = 10): control, CI/R and CI/R+Agomelatine (20 and 40 mg/kg). In groups other than control, 60-minute CI was applied. One hour after SI, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, and 20 and 40 mg/kg Agomelatine was administered to the SI/R+Agomelatine groups. During three days of R, the rats were subjected to NDS, rotarod, adhesive removal and gip strength tests. At the end of the experiment, the animals were decapitated and their brain tissues were taken. In the brain tissues taken, the levels of infarct area were determined by TTC staining method, and the levels of apoptosis (BCL-2 and BAX) and autophagy (Beclin-1, ATG5, ATG7 and p62) proteins were determined by Western Blot method. Statistical analysis of the data obtained was performed. Results: Control and Agomelatin groups than CI/R group, adhesive removal time and NDS score were lower; rotarod time and grip strength were higher (p<0.05). The infarct area was determined to be larger in the CI/R group compared to the control and SI/R+Agomelatine groups (p<0.05). BCL-2, Beclin-1, ATG5 and ATG7 protein levels were found to be higher in the SI/R+Agomelatine group compared to the CI/R group, and BAX and p62 protein levels were found to be lower (p<0.05). Conclusion: Agomelatine was observed to reduce the neurological deficit score. In behavioral tests, it was determined that it improved balance-motor coordination, somatosensory and strength loss. Additionally, it was determined that Agomelatine reduced the infarct area caused by CI/R injury. In addition, it was determined that it affected the apoptotic protein levels in a way that would inhibit apoptosis and the autophagic protein levels in a way that would induce autophagy.