Indian Journal of Science and Technology

Abstract

Objectives: To study the effect of NG nitro L Arginine Methyl Ester (L-NAME) on anxiety, cognition, motor activity and neuronal damage when administered pre, during and post ischemically in rats. Methods: L-NAME was administered 30 minutes before inducing ischemia (Preischemic), 1 hour after ischemia (During ischemic) and 3 hours after reperfusion (Post ischemic). After 72 hours of reperfusion, animals were assessed for anxiety using elevated plus maze test, cognition using Y-maze test and motor activity using beam walk and rota rod test. Rats were euthanized using carbon di oxide and the brains were collected. Neuronal damage was studied in the brain sections using hematoxylin and eosin stained brain sections. Findings: Pre ischemic administration of L-NAME has increased the time spent (p<0.001) and number of entries (p<0.01) into the open arm in the elevated plus maze than during and post ischemic administration. In the Y-maze test, pre ischemic administration of L-NAME has increased the time spent (p<0.001) and number of entries (p<0.05) in the open arm than start and novel arm. During and post ischemic administration of L-NAME has increased the time spent in open arm (p<0.05) however there was no change in the number of entries into the open arm. In the rota rod test, pre ischemic administration of L-NAME had significantly increased the fall time than (p<0.001). A non significant increase in the fall time was observed in the rota rod test in the during and post ischemic group. In the beam walk test, time taken to reach the goal box (p<0.01) and the number of foot faults (p<0.001) were decreased significantly in the pre ischemic L-NAME group than during and post ischemic administration. Pre ischemic administration of L-NAME has also significantly reduced the percentage neuronal damage. Novelty of the study: Though the effect of L-NAME on middle cerebral artery occluded / reperfused rats has been demonstrated in many previous studies, it fails in the clinical trials due to the lack of knowledge on appropriate therapeutic time window. In the current study, the appropriate therapeutic time window of L-NAME has been determined by administering L-NAME at three different time points i.e. pre, during and post ischemic / reperfusion. Conclusion/Application: L-NAME when administered pre ischemically, exerts anxiolytic effect, improves cognition and motor activity.
Keywords: Behaviour, Cerebral Ischemia, Excitotoxicity, L-NAME, Middle Cerebral Artery Occlusion / Reperfusion, Motor Activity