Long-term and spatial memory effects of selective β1-antagonists after transient focal ischaemia in rats

Abstract

Although various reports have shown that β-antagonists provide neuroprotective effects after cerebral ischaemia, their effect on spatial memory after transient focal ischaemia is not known. We investigated the treatment of β1-antagonists on neurological outcome spatial memory for 1 month after focal cerebral ischaemia in rats. Male rats randomly received an i.v. infusion of saline 0.5 ml h(-1), esmolol 200 μg kg(-1) min(-1), or landiolol 50 μg kg(-1) min(-1). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. The infarct areas in the hippocampus and striatum were measured after the final retention trial and neurological examinations. Neurological deficit scores in the landiolol- and esmolol-treated rats were significantly lower than in the control rats at 1, 4, 7, and 11 days after ischaemia (P<0.05). Using the Morris water maze to assess spatial memory, we found that escape latency and swimming path length to the platform were significantly shorter in the landiolol-treated rats, compared with the saline-treated rats at 4 and 11 days after ischaemia (P<0.05). The mean (SD) infarct area was 19.1 (8.0)% in the striatum and 18.6 (10.0)% in the hippocampus of the landiolol-treated rats, and 16.8 (14.0)% and 16.8 (15.0)% in the striatum and hippocampus, respectively, of esmolol-treated rats. This was significantly less than in control rats [striatum 31.7 (14.0)% and hippocampus 29.8 (13.0)%, P<0.05]. The current study indicates that although esmolol and landiolol provided long-term neuroprotection in terms of histological outcome, they had no effect on neurological outcome and spatial memory retention.