Effect of bis(7)-tacrine on cognition in rats with chronic cerebral ischemia

Bis(7)-tacrine (B7T), a novel dimeric acetyl cholinesterase (AChE) inhibitor, has multiple neuroprotective activities against neuronal damage. However, its therapeutic effects in chronic cerebral ischemia remain unknown. In the present study, adult male Sprague-Dawley rats were subjected with permanent ligation of the bilateral common carotid arteries to investigate the roles of B7T on cognitive function, neuronal apoptosis and neurogenesis in the hippocampus. Results from spatial navigation test showed that chronic cerebral ischemia impaired spatial learning, B7T treatment shorten escape latency of ischemia rats as compared with saline-treated rats. Probe trial test indicated that spatial memory deficit of chronic cerebral ischemic animals was reversed by B7T treatment. Immunohistochemical results showed that B7T reduced neuronal apoptosis in the hippocampal CA1 region as compared with ischemia rats, and B7T treatment increased neurogenesis in the hippocampus. These findings suggest that B7T may exert its neuroprotective effects by inhibiting apoptosis and promoting neurogenesis in 2VO rats.

► B7T has multiple neuroprotective activities against neuronal damage.
► We evaluate effects of bis(7)-tacrine (B7T) on chronic cerebral ischemia rats.
► B7T restores cognition impairment induced by chronic cerebral ischemia.
► B7T reduces neural apoptosis in hippocampal CA1 region of ischemia rats.
► B7T promotes neurogenesis in hippocampal DG of ischemia rats.