Study on protective effects of minocycline on memory deficits after cerebral ischemia due to transient bilateral occlusion of common carotid arteries in rat

Spatial memory and learning deficits are the most visible symptoms of transient cerebral ischemia. Cortex and hippocampus are sensitive against cerebral ischemia. Oxidative stress and inflammation are involved in the pathological process after cerebral ischemic injury. Evidence indicates that minocycline has antioxidant and anti-inflammation effects. In this study the effect of minocycline on memory deficit after transient cerebral ischemia in rat was investigated.

Cerebral ischemia was induced by a transient 20 min bilateral occlusion of common carotid artery (BOCCA) of rat. A total of 60 male Wistar rats weighing 250-300 g were divided into 6 groups. Three groups of rats were evaluated for each drug administration method (pre- or post-ischemic administration of drug or vehicle). 1. Sham group: rats were subjected to the surgical procedure except for occlusion of common carotid artery and received saline (vehicle) 24 h before, or twice daily (every 12 hours) for 7 days after surgery; 2. Control group: rats underwent transient BOCCA and saline was injected 24 h before or twice daily for 7 days after ischemia; 3. Minocycline group: minocycline (40 mg/kg, i.p.) was injected 24 h before I/R (single dose), or twice daily, for 7 days after I/R. The spatial memory and learning were evaluated using the Morris water maze task.

Pre- or post-ischemic administration of minocycline significantly shortened the escape latency time and the distance traversed to reach the hidden platform. It also significantly increased the time spent in target quadrant compared with the control group. There was no significant change in the swimming speed of rats after I/R in the control and minocycline groups (either pre- or post-ischemic administration) during the first 4 days (trial) and the fifth day (probe test).

This study demonstrated the effectiveness of minocycline in preventing spatial memory and learning deficits induced by cerebral ischemia.