ro-25-6981 and Cognition-Disorders

Approximately 50% of patients who survived after aneurysmal subarachnoid hemorrhage (SAH) have cognitive or neurobehavioral dysfunction. The mechanisms are not known. NR2B, one of the subunits of N-methyl-d-aspartate (NMDA) receptors, has been proved to be an important factor for synapse function and behavior cognition. Experiment 1 aimed to investigate the timecourse of the NR2B expression in the cortex, hippocampus, and cerebellum after SAH in rats. In experiment 2, we assessed the effect of Ro 25-6981 (a specific NR2B antagonist) on regulation of learning deficits and behavioral activity following SAH. All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once on day 0. NR2B was assessed by Western blot analysis and immunohistochemistry. Cognitive and memory changes were investigated in the Morris water maze. As a result, the expression of NR2B was decreased remarkably in SAH groups compared with the control group and the low ebb was on days 1-3. The immunohistochemical staining demonstrated expression of NR2B was present mainly in the neurons in all of the three different regions, such as the cortex, hippocampus, and cerebellum. After Ro 25-6981 intraperitoneal administration, learning deficits induced by SAH was markedly aggravated and clinical behavior scale was also significantly decreased. Our results suggest that NR2B expression is down-regulated in the brain after experimental SAH and NR2B antagonism resulted in augmentation of the development of cognitive dysfunction after SAH.

Topics: Animals; Behavior, Animal; Cerebellum; Cerebral Cortex; Cognition Disorders; Disease Models, Animal; Down-Regulation; Hippocampus; Maze Learning; Neurons; Phenols; Piperidines; Rats; Receptors, N-Methyl-D-Aspartate; Subarachnoid Hemorrhage