Hypertension is one of the major risk factors for central nervous system (CNS) 
disorders like stroke and Alzheimer's disease (AD). On the other hand, CNS 
diseases like AD have been associated with gliosis and impaired neurogenesis. 
Further, renin angiotensin system (RAS) is intricately associated with 
hypertension; however, the accumulating evidences suggest that over-activity of 
RAS may perpetuate the brain inflammation related with AD. Therefore, in the 
present study, we examined the effect of hypertension and RAS on glial 
(astrocytes and microglia) activation and hippocampal neurogenesis in a rat 
model of chronic hypertension. We used Candesartan [angiotensin type 1 receptor 
(AT1R) blocker (ARB)] both at a low dose (0.1 mg/kg) and anti-hypertensive dose 
(2 mg/kg) to explore whether their effect on astrocyte and microglial 
activation, neuroinflammation, and neurogenesis is blood pressure (BP) dependent 
or independent. Our data revealed that hypertension induces robust microglial 
and astrocyte activation, neuroinflammation, and cripples hippocampal 
neurogenesis. Importantly, AT1R blockade by Candesartan, even at low dose 
(0.1 mg/kg), prevented astrocyte and microglial activation and neuroinflammation 
in the brain of hypertensive rats. Mechanistically, AT1R blockade prevented the 
activation of NADPH oxidase, reactive oxygen species (ROS) generation, 
suppression of MAP kinase and NFкB signaling. Importantly, we, for the first 
time to our knowledge, provided the evidence that AT1R blockade by activating 
Wnt/β-catenin signaling, promotes neurogenesis during hypertensive state. We 
conclude that AT1R blockade prevents astrocyte and microglial activation and 
improves hippocampal neurogenesis in hypertensive state, independent of BP 
lowering action.