Angiotensin type 1 receptor blockers (ARBs) have induced improved functional recovery and reduced
infarct volume in experimental animal models of
stroke. Clinical data have indicated a positive correlation between prestroke treatment with ARBs and reduced
stroke severity and better outcomes; however, the mechanisms of these beneficial effects are not yet well understood. This study compares the protective and possible reparative effects of continuous oral treatment with
olmesartan (OLM) with OLM pretreatment and withdrawal after permanent
middle cerebral artery occlusion (pMCAO) in rats. Fifty-two Sprague-Dawley rats were randomly assigned to five groups: MCAO(-/OLM) (OLM 10 mg/kg/day for 14 days after
infarct), MCAO(OLM/OLM) (OLM 10 mg/kg/day for 7 days before and 14 days after
infarct), MCAO(OLM/-) (OLM 10 mg/kg/day for 7 days before
infarct),
sham, and control. We analyzed functional recovery; lesion size; cell death; expression of the
pro-oxidant enzyme NADPH oxidase 4 (NOX-4);
isolectin-B4; and repair markers such as
glial fibrillary acidic protein,
vascular endothelial growth factor (
VEGF), and
brain-derived neurotrophic factor (
BDNF). All of the OLM-treated groups showed significantly better functional scores and reduced
infarct sizes and cell death compared with the control group 14 days after pMCAO. Levels of NOX-4,
VEGF, and
BDNF were significantly lower in the brains of the MCAO(OLM/OLM) and
sham groups compared with the other groups. OLM treatment improved functional recovery and reduced lesion size and cell death after
cerebral ischemia. Only the continuous administration of OLM before and after
stroke reduced oxidative stress levels, with better tissue preservation, without triggering brain repair marker activation.