The Effects of AT010 on Behavioral Compensation After Cerebral Ischemia in the Rat
Release of glutamate in cerebral ischemia results in an excitotoxic reaction in the central nervous system resulting in neuronal cell loss. Providing neuronal protection via N‐methyl D‐asparate (NMDA) receptor blockade in response to cerebral ischemia may result in preservation of function following ischemia. The present study was designed to test compound AT010, an NMDA signaling antagonist, on behavioral compensation and infarct size in a cerebral ischemia model in the rat. Animals were surgically implanted with a filament via the external carotid artery, providing an occlusion of he medial cerebral artery for 60 min. Approximately 30‐45 minutes prior to surgery, the compound AT010 (3uM or 10uM) or saline was iv administered at 1% of body weight. All animals were behaviorally tested on behavioral tasks that analyzed postural reflex, limb placement, righting reflex, adhesive removal, and behavioral motor function at 3, 7, and 14 days post‐ischemia. In addition, animals were tested on the Morris water maze, a spatial memory task 28 days post‐ischemia. Regardless of dose, composite neurological scores for all motor and sensory tasks were higher for animals given AT010 compared to saline at 7 and 14 days post‐ ischemia. Water maze results revealed significant improvement of animals administered the higher dose of AT010 (10uM) on acquisition and probe trial performance, although no effect was revealed for the lower dose (3 uM). Finally, analysis of brain tissue samples revealed no significant effect on infarct size. These results indicate that compensation occurred throughout the undamaged brain areas, likely through synaptic communication changes as a result of drug treatment.
Kassem, G. L.; Cummins, Elizabeth D.; Peterson, Daniel J.; and Brown, Russell W.. 2014. The Effects of AT010 on Behavioral Compensation After Cerebral Ischemia in the Rat. SYNAPSE Conference, Asheville, NC. https://blogs.cofc.edu/synapse/files/2016/01/2014-abstracts-final-10qk03k.pdf