Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

Abstract

Metabolic diseases including obesity, insulin resistance, and diabetes have profound effects on cerebral circulation. These diseases not only affect the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression but also alter the physiology of blood vessels resulting in compromised myogenic reactivity, neurovascular uncoupling, and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain rapidly occur. This overview is organized into sections describing cerebrovascular architecture, physiology, and BBB in these diseases. In each section, we review these properties starting with larger arteries moving into smaller vessels. Where information is available, we review in the order of obesity, insulin resistance, and diabetes. We also tried to include information on biological variables such as the sex of the animal models noted since most of the information summarized was obtained using male animals. © 2018 American Physiological Society. Compr Physiol 8:773-799, 2018.

Obesity in Midlife Hampers Resting and Sensory‐Evoked Cerebral Blood Flow in Mice

“…Physiological aging as well as HFD duration also induced a decrease in odor-evoked CBF. These results revealing neurovascular uncoupling are in line with previous observations showing (i) a decrease in visually evoked functional hyperemia recorded by functional magnetic resonance imaging in people with obesity and type 2 diabetes (32) and in lean, older individuals (33) in clinics and (ii) a decrease in sensory-evoked CBF in the somatosensory cortex of young-adult and older obese rodents (10,(14)(15).…”

Impaired endothelium-mediated cerebrovascular reactivity promotes anxiety and respiration disorders in mice

“…Thus, short and rapid vascular responses to even small changes in blood CO 2 levels control normal brain function, at least in CO 2 -sensitive areas. Impaired cerebrovascular reactivity to CO 2 is a key diagnostic feature of endothelial dysfunction (39) that develops in metabolic syndrome and in several vascular diseases (60). Our data suggest that endothelial dysfunction in the brain contributes to the pathogenesis of sleep apnea and anxiety disorders, and maybe other diseases that are often associated with metabolic syndrome (29,30,34).…”

NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia

“…The two main settings in which VCID occur are 1) post-stroke, in which cognitive impairment results due to ischemic injury, and 2) without recent stroke, in which injury manifests through neuropathology rather than stroke [56]. We have previously reported vascular contributions to cognitive impairment and worsened outcome after ischemia in the cortex and striatum [45,47,48,[57][58][59]. In the present study, we further support these findings in the hippocampus, an area remote to the site of injury.…”