Abstract WMP37: Neurovascular Protection by Telmisartan Via Reducing Neuroinflammation in SHR-SR Brain After Ischemic Stroke

Telmisartan is a highly lipid soluble angiotensin receptor blocker (ARB) which improves insulin sensitivity and reduces triglyceride levels, thus is called metabo-sartan. We examined effects of telmisartan on neurovascular unit (NAGO, collagen IV, and GFAP) and neuroinflammation (MMP-9 and inflammasome) in brain of stroke-resistant spontaneously hypertensive rat (SHR-SR). At 12 weeks of age, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 min, and were divided into the following 3 groups, i.e., vehicle group, low-dose telmisartan group (0.3 mg/kg/day), and high-dose telmisartan group (3 mg/kg/day, p.o. ). Immunohistological analysis at ages 6, 12 and 18 months showed progressive decreases of NAGO-positive endothelium and collagen IV positive basement membrane, and progressive increases of MMP-9-positive neurons, GFAP-positive astrocytes, and NLRP3-positive inflammasome in the cerebral cortex of vehicle group. Low dose telmisartan reduced such changes without lowering blood pressure (BP), and high dose telmisartan further improved such changes with lowering BP. The present findings suggest that a persistent hypertension caused a long lasting inflammation after tMCAO in SHR-SR which accelerated neurovascular disruption and emergent inflammasome, and that telmisartan greatly reduced such inflammation and protected the neurovascular unit via its pleiotropic effects in living hypertensive rat brain after ischemic stroke.