Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Jun 2014
Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction.
Postoperative cognitive dysfunction (POCD) is a common geriatric complication, although its exact neuropathogenesis remains elusive. Blockers of the renin-angiotensin system (RAS) ameliorate cognitive deficits in inflammatory brain disorders, with its effects on POCD not yet fully elucidated. The aim of the present study was to investigate regulation of the brain RAS and the effect of angiotensin II receptor type 1 (AT1) inhibition on surgery-induced cognitive impairment in a well-established rat POCD model. ⋯ Concomitant with these functional benefits, we observed significant inhibition of hippocampal neuroinflammation, evidenced by decreased glial reactivity and phosphorylation of the NF-κB p65 subunit, as well as marked reductions in interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. Our results are the first to show that activation of the brain RAS after surgery contributes to POCD in aged rats. Chronic treatment with low doses of candesartan may elicit blood pressure-independent neuroprotective effects in POCD by improving BBB function and promoting resolution of neuroinflammation.