l-NAME combats excitotoxicity and recuperates neurological deficits in MCAO/R rats

Since, transient focal cerebral ischaemia exhibits detrimental effect not only during the course of ischaemia but also after the onset of reperfusion, the current study is focussed on identifying the appropriate therapeutic time point at which NG-nitro-l-arginine methyl ester (l-NAME) exerts better neuroprotection. Pre-ischaemic administration of l-NAME ameliorated neurological deficits much better than the during ischaemic and post-ischaemic groups. Pre-ischaemic l-NAME has also mitigated glutamate excitotoxicity, increased glutamine synthetase activity, ATP and NAD levels, decreased nitrate/nitrite content, down regulated TNF-α and upregulated IL-10 expressions and reduced the cerebral infarction significantly than the during ischaemic and post-ischaemic groups. Current study revealed that l-NAME improved neurological deficit at the pre-ischaemic state in transient focal cerebral ischaemia and has also significantly ameliorated glutamate excitotoxicity. Though l-NAME showed neuroprotective effects when administered at during and post-ischaemia (during reperfusion), it exerts considerable neuroprotection when administered pre-ischaemically. •l-NAME improves neurological functioning when administered prior to ischaemia.•l-NAME mitigates excitotoxicity, augments ATP & NAD levels and reduces nitrate/nitrite in the brain.•l- NAME reduces brain infarction size.•l-NAME exerts better neuroprotection when administered prior to ischaemia than during and post-ischaemia.