Interaction between hypertension and cerebral hypoperfusion in the development of cognitive dysfunction and white matter pathology in rats

•Hypertensive rats developed earlier and more severe deficits in spatial memory after BCCAO than normotensive rats.•Subtle myelin degeneration and paranodal structural alteration were noted after BCCAO regardless of hypertension.•BBB disruption of the blood-brain barrier was predominantly observed in the white matter of SHRs after BCCAO.•Hypertension may significantly affect cognitive dysfunction in white matter ischemia by inducing BBB impairment.

Hypertension is the most significant modifiable risk factor for vascular cognitive impairment. However, influence of hypertension on the development of ischemic white matter injury and cognitive dysfunction is not fully understood. We compared cognitive functions and neuropathological outcomes of chronic cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAO) between normotensive rats (NRs) and spontaneously hypertensive rats (SHRs). SHRs developed earlier and more severe deficits in spatial memory performance than NRs following BCCAO. Although no significant changes in the gross structure of myelinated white matter or oligodendrocyte number were noted, BCCAO resulted in subtle myelin degeneration and paranodal structural alterations at the nodes of Ranvier, regardless of hypertension. Disruption of the blood-brain barrier (BBB) was predominantly observed in the white matter of SHRs following BCCAO, implying a role of hypertension in BBB dysfunction in chronic cerebral hypoperfusion. In chronic cerebral ischemia, long-standing hypertension may aggravate impairment of BBB integrity, and the leaky BBB may in turn exacerbate dysfunction in the white matter leading to worsening of spatial cognitive performance.