Treatment of aged mice with the mitochondria targeted antioxidative peptide SS‐31 protects against hypertension‐induced cerebral microhemorrhages

Abstract

Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 mo) and aged (24 mo) mice were treated with angiotensin‐II plus L‐NAME. We found that the same level of hypertension led to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis and histological assessment of CMHs in serial brain sections. Our data suggest that aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. We found that hypertension increased mitochondrial free radical production in the wall of cerebral arteries. Treatment of aged mice with the mitochondria‐targeted antioxidative tetrapeptide SS‐31 exerted significant vasoprotective effects and significantly delayed the onset and reduced the incidence of CMHs. Thus, therapeutic strategies that reduce mitochondrial oxidative stress may be useful for the prevention of CMHs in the aged brain.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.