Effects of Renin-Angiotensin System Inhibition on Ischemic Brain Edema Formation and Blood-Brain Barrier Disruption Following Focal Cerebral Ischemia in Rat

Ischemic brain edema is one of the most important complications of cerebral infarction. Edema aggravates the primary ischemic injury to the brain. It was demonstrated that the renin-angiotensin system (RAS) and its active peptide angiotensin II involved in ischemic brain injury. But role of RAS in the formation of ischemic edema is not clear. The present study was conducted to investigate the effects of the RAS inhibition by enalapril on edema formation and blood-brain barrier (BBB) disruption. In this research frothy Sprague Dawley male rat in six groups were studied. Animals were anesthetized with chloral hydrate (400mg/kg, IP). Transient focal cerebral ischemia was induced by occlusion of right middle cerebral artery using intraluminal filament method. Three groups of animals as sham, ischemic and enalapril receiving (0.03mg/kg) groups were studied for assessment of neurological outcome and brain edema formation. 24 hours following ischemia (60minutes), animals were assessed for neurological deficits. Ischemic brain edema was investigated by brain water content detection. Another three groups of animals at the same conditions were studied to evaluate the possible disruption of BBB by Evans blue extravasation technique. When sham operated rats had no motor deficit, induction of ischemia in ischemic group, seriously caused impairment of motor functions and neurological deficit score(NDS) of ischemic group was 2.67±0.42. Pretreatment with enalapril (0.03mg/kg) significantly reduced NDS and improved motor dysfunctions (1.5±0.34, P <0.05). Induction of ischemia seriously caused edema formation in right (ischemic) hemisphere of the brain in ischemic group (4.1±0.4 percent). Pretreatment with enalapril (0.03mg/kg) significantly decreased edema compared to ischemic group (1.89±0.23 percent). Extravasation of Evans blue in right side of the brain in ischemic group (12.48±1.94 μg/g) was significantly more than sham group. Pretreatment with enalapril (0.03mg/kg) had protective effects on BBB function and decreased Evans blue extravasation by 44.5 percent (6.92±1.46 μg/g). RAS inhibition by enalapril reduces ischemic brain edema formation by protecting the integrity of BBB and reducing its permeability following focal cerebral ischemia in rat. Pre-ischemic inhibition of RAS activity may reduce ischemic brain injury by ameliorating edema formation.