Impact of diabetes and ischemic stroke on the cerebrovasculature: A female perspective

Abstract

There is a very complex interaction between the brain and the cerebral vasculature to meet the metabolic demands of the brain for proper function. Preservation of vascular networks and cerebrovascular function ultimately plays a key role in this intricate communication within the brain in health and disease. Experimental evidence showed that diabetes not only affects the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression, but also alters cerebrovascular function resulting in compromised myogenic reactivity and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain can rapidly occur. When an ischemic insult is superimposed on this pathology, not only is the neurovascular injury greater, but repair mechanisms fail, resulting in greater physical and cognitive deficits. While clinically it is known that women suffer disproportionately from diabetes as well as ischemic stroke and post-stroke cognitive impairment, the cerebrovascular architecture, patho/physiology, as well as cerebrovascular contributions to stroke recovery in female and diabetic animal models are inadequately studied and highlighted in this review.

Keywords: Cerebrovasculature; Diabetes; Sex differences; Stroke; Vascularization.

Figure 1.

There are sex differences in the angioarchitecture of female and male mice. MicroCT analysis of cerebrovascular corrosion casts revealed greater intervessel distance in males whereas females exhibited greater vascular density. (Reproduced with permission from ref 9).

Figure 2.

Cerebral vascularization in the frontal cortex of female and male rats exhibit sex differences in diabetes and after stroke. Diabetes promotes pathological angiogenesis in male rats whereas there are no changes in vascularization patterns in diabetic female rats as compared to controls. Ischemic stroke triggers reparative angiogenesis in control male rats whereas diabetic male rats develop vasoregression characterized by regulated endothelial cell death by Day 14 after stroke. In female control rats, stroke does not affect vascularization status, but diabetic female rats show phenotypic changes characteristic of endothelial mesenchymal transition.