The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours days following restoration of spontaneous circulation. This study aimed examine protective and/or therapeutic effects cerebrolysin (CBL) managing forebrain IR any probable underlying mechanisms. To contribution reperfusion injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups six BLC57 mice were created: Group 1: control group (no surgery was performed); 2: sham (surgery performed without IR); 3: tDCAL/IR with via permanently ligating left CA temporarily closing right for 30 min, followed by 72 h); 4: CBL + (CBL given intravenously at 60 mg/kg BW dose min before 5: administered i.v. three after IR). At h IR, euthanized. administration 3 improved functional recovery, enhanced anti-inflammatory antioxidant activities, alleviated apoptotic neuronal death, inhibited reactive microglial astrocyte activation, resulting neuroprotection as compared other groups. Furthermore, reduced TLRs/NF-kB/cytokines while activating Keap1/Nrf2/antioxidant signaling pathway. These results indicate that may improve neurologic function IR.