Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death in industrialized countries. It is suggested that renin–angiotensin system (RAS) may contribute in stroke related pathogenic mechanisms and involve in the ischemic brain damage. This study designed to investigate the role of angiotensin II (Ang II) in conjunction with AT₁ receptors in treatment of the brain injuries following transient focal cerebral ischemia in rats.

  Methods: Forty eight male Sprague-Dawley rats were studied in four groups. Sham group, ischemic control group and two ischemic groups that received candesartan (0.1mg/kg, or 0.5mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 hours reperfusion. At the end of the reperfusion period, neurological deficit score (NDS) was performed. Total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride (TTC) staining technique.

  Results: Animals in sham operated group had normal motor function and no ischemic lesions were observed in cortical or striatal regions. Occurring ischemia in ischemic control group that received vehicle produced considerable infarction in cortex (253±15mm³) and striatum (92±7mm³), as well as these animals had sever impaired motor dysfunctions. Blocking of AT1 receptors with candesartan (0.1mg/kg or 0.5mg/kg) improved neurological outcome and significantly lowered cortical and striatal infarct volumes relative to ischemic control group.

  Conclusion: The findings of the present study indicated that stimulation of AT1 receptors by Ang II involved in ischemia/reperfusion injuries and blocking of AT1 receptors can decrease ischemic brain injury and improve neurological outcome.

Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. Several experimental studies have shown that combination therapy with drugs that act via different mechanisms can produce amplified protective effects. We examined the effects of combination therapy with candesartan and alpha tocopherol against cerebral ischemia.

Methods: Male Sprague-Dawley rats were divided into five groups (n=24): sham, control ischemic, candesartan treated (0.3 mg/kg), alpha tocopherol treated (30 mg/kg) and combined treated ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly used for measurement of the infarct volumes and investigation of ischemic brain edema formation using a wet/dry method.

Results: Induction of cerebral ischemia produced considerable brain infarction in conjunction with severely impaired motor functions and edema formation. Combined treatment with candesartan and alpha tocopherol significantly reduced the infarct volume and lowered the water content in the ischemic lesioned hemisphere. These effects on brain edema and oxidative stress biomarkers were significantly more than the monotherapy with candesartan.

Conclusion: The combination therapy with candesartan and alpha tocopherol can noticeably decrease ischemic brain injury and attenuate edema formation likely via increasing the antioxidant activity.