Pretreatment with bisoprolol and vitamin E alone or in combination provides neuroprotection against cerebral ischemia/reperfusion injury in rats

Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in the hippocampus, leading to severe impairment in
behavior, learning, and memory functions. This study aimed to evaluate the neuroprotective effects of bisoprolol (biso) and
vitamin E (vit E) treatment alone or in combination on cerebral ischemia/reperfusion (I/R) injury. A total of 30 male rats were
divided randomly into five groups (n = 6), sham, I/R, I/R + biso, I/R + vit E, and I/R + biso+vit E. Cerebral I/R group underwent
global ischemia by bilateral common carotid artery occlusion for 20 min. Treatment groups received drugs once daily intraperitoneally
for 7 days before the I/R induction. Locomotive and cognitive behaviors were utilized by open-field and Morris water
maze tests. After behavioral testing, the brain was removed and processed to evaluate cerebral infarct size, histopathologic
changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) level. In I/R group tissue MDA and MPO levels and
cerebral infarct size were significantly increased in comparison with the sham group. Furthermore, significant deficits were
observed in locomotion and spatial memory after I/R. The areas of cerebral infarction, MPO, and MDA levels in biso, vit E, and
combination group were significantly reduced compared with I/R group. Histopathological analysis demonstrated a significant
reduction in leukocyte infiltration in all treated groups with the most profound reduction in the combination group. According to
the behavioral tests, administration of biso and/or vit E protected locomotive ability and improved spatial memory after cerebral
I/R. Our findings show that biso and vit E have beneficial effects against the I/R injury and due to their synergistic effects when
administered in combination, may have a more pronounced protective effect on the cerebral I/R injury.