Post-stroke effects of IC87201 on neurobehavioral function and brain injuries: A stereological study

Stroke is the second leading cause of global death and is characterized by excitotoxic neuronal death caused by NMDA (N-Methyl-D-Aspartate) receptor overactivation. The present study was conducted to investigate the therapeutic potential of IC87201, a novel small molecule interfering with the NMDA receptor intracellular signaling pathway, in reducing the extent of ischemic stroke-induced brain damage. Cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) method in 24 anesthetized adult male rats for one hour. The animals were randomized into sham, MCAO, MCAO+ DXM (Dextromethorphan hydrobromide monohydrate) as an NMDA antagonist, and MCAO+ IC87201 groups which in the last two groups, DXM (50 mg/kg) and IC87201 (10 mg/kg) were injected intraperitoneally after ischemia. The neurobehavioral scores were appraised for 7 days and after that, brain tissue was appropriately prepared to perform the stereological evaluations. The administration of IC87201 significantly recovered post-ischemia damages, including neurobehavioral function, reduction of volume of the total hemisphere, cortex, and striatum in rat brain, and the percentage of infarcted areas. Additionally, in the striatum region, IC87201 caused an increase in the total number of neuronal and non-neuronal cells as well as a decrease in the total number of dead cells. Some of these parameters were improved by DXM, but in general, IC87201 outperformed that. IC87201 was successful in minimizing ischemia-induced damage, especially in the striatal region. In addition, IC87201, as a molecule that acts on the intracellular signaling cascade of the NMDA receptor, performed better than DXM, as an antagonist of this receptor. •Ischemic stroke in the striatum destroys neurons and non-neuronal cells•Ischemic stroke in the striatum impairs the motor and sensory functions.•IC87201 remarkably improves post-stroke striatal injuries and behavioral deficits.•IC87201 had more beneficial effects on stroke than DXM, an NMDA receptor antagonist.