Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

Abstract

The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs.

Chronic PARP-1 inhibition reduces carotid vessel remodeling and oxidative damage of the dorsal hippocampus in spontaneously hypertensive rats

“…Long term L-2286 treatment aided preserving structure of vessels in this area. Compromised barrier function and perturbations in the supply of neuronal tissue leads to the activation of astroglia population evident in young SHR animals by the elevated expression of GFAP in different brain areas, compared to their normotensive counterparts [36, 38, 74]. Regarding this process, in our study we found an increase in the average size of reactive astrocita in the hippocampal fissure of SHR-C animals (Fig 3H), without hyperplasic differences between the strains.…”

“…Brains of SHR animals show well-described pathologies related to chronic hypertension, which make these animals a feasible model for studying target organ damages [36, 74]. A vasogenic oedema related dilatation of the cerebral ventriculi was observed [75].…”

“…Also, hypertension induced structural remodeling of main arteries is also present in the cerebrovascular system of SHR animals, in connection with microvascular changes [2, 36, 37]. It compromises proper oxygen and nutrient supply of neuronal tissue, creating an ischaemic environment [74, 78]. Additionally, on a genetic background, SHR animals have impaired resistance against cerebral ischaemic insults early in life [79], predisposing this strain to augmented tissue damage in chronic hypertension.…”

Selective Oestrogen Receptor Agonists Rescued Hippocampus Parameters in Male Spontaneously Hypertensive Rats

“…Among the affected regions, the hippocampus appears to be highly vulnerable to hypertension. Thus, typical findings in SHR hippocampus include neuronal degeneration, necrosis and apoptosis, amyloidosis and tau pathology, atrophy of dendrites, low spine number and abnormal neurogenesis . Hippocampal damage accelerates with time, as shown by increased oxidative stress and expression of apoptotic markers in the hippocampus of ageing SHR .…”

“…Thus, typical findings in SHR hippocampus include neuronal degeneration, necrosis and apoptosis, amyloidosis and tau pathology, atrophy of dendrites, low spine number and abnormal neurogenesis . Hippocampal damage accelerates with time, as shown by increased oxidative stress and expression of apoptotic markers in the hippocampus of ageing SHR . In the hypothalamus, SHR show increased expression of the hypertensinogenic peptide arginine vasopressin and its V1b receptor, contributing to hypertension impairment .…”