Abstract WP297: Moderate Alcohol Preconditioning Activates BKCa Channels to Protect Brain Damage-Induced by Cerebral Ischemic/Reperfusion

Abstract

Objective: We hypothesis that moderate EtOH-PC activates BKCa channel to protect brain damage induced by focal cerebral I/R. This project will utilize focal cerebral ischemic/reperfusion (I/R) animal model to explore the function of BKCa channel in EtOH-PC protection in vivo levels by means of pharmacological intervention such as BKCa channel opener(NS11021)and blocker(Paxilline). Methods: The SD rat were randomly divided into the following six groups (n=10) : sham, I/R ,EtOH-PC+I/R, NS11021-PC+I/R, Paxilline+EtOH-PC+I/R, Paxilline+NS11021-PC+I/R. Both EtOH-PC and NS11021-PC (0.1mg/kg; ip) were induced 24h before I/R. The volume of 95% ethanol to be instilled (in μL) was calculated as follows: [body weight (g)х0.6] + 0.3. This volume of ethanol was mixed in 0.3mL of sterile distilled water just before administration to the animals by gavage. The Paxilline(2.5mg/kg; ip) was administered 10min before EtOH-PC and NS11021-PC.The right middle cerebral artery occlusion (MCAO) was produced by inversion of a 4-0-nylon filament. The filament was withdrawn 2h after onset of MCAO and then reperfused. Neurological deficits and infarct volume were measured 24 hours after I/R. Another 36 rats were randomly divided into 6 groups as above, 6 in each group. DWI were performed 2h after ischemic and T2WI MRI were performed 24h after ischemic/reperfusion to observe the infarct volume of brain and the penumbra volume of brain in each group. Then rats were killed and detected the apoptotic cell death and degeneration of neurons. Results: Compared to ischemic-reperfusion group, the neurological score (P < 0.01), the infarct volume of brain (P < 0.01), the infarct volume of ischemic penumbra(P < 0.01),the percentage of apoptotic cell death (P < 0.01) and the percentage of degenerative neurons (P < 0.01) were significantly decreased after ethanol and NS11021 preconditioning,while these changes were reversed by Paxilline(P < 0.05). Conclusion: Our results show that moderate alcohol preconditioning activates BKCa channels to protect brain damage induced by focal cerebral ischemic/reperfusion.