Circadian Biology and the Neurovascular Unit

Abstract

Mammalian physiology and cellular function are subject to significant oscillations over the course of every 24-hour day. It is likely that these daily rhythms will affect function as well as mechanisms of disease in the central nervous system. In this review, we attempt to survey and synthesize emerging studies that investigate how circadian biology may influence the neurovascular unit. We examine how circadian clocks may operate in neural, glial, and vascular compartments, review how circadian mechanisms regulate cell-cell signaling, assess interactions with aging and vascular comorbidities, and finally ask whether and how circadian effects and disruptions in rhythms may influence the risk and progression of pathophysiology in cerebrovascular disease. Overcoming identified challenges and leveraging opportunities for future research might support the development of novel circadian-based treatments for stroke.

Circadian Mechanisms in Cardiovascular and Cerebrovascular Disease

“…The central importance of circadian biology is perhaps best appreciated by understanding how daily rhythms seem to control function in all cell types in the mammalian brain. Hence, Li et al 18 provide a review of how circadian rhythms may mediate and integrate function in various cells of the neurovascular unit. The section on the brain then concludes with a translational review from Mergenthaler et al 19 who argue the case that because diurnal rhythms play such a fundamental role in brain health, any therapies for stroke cannot be optimized unless the impact of circadian time and the potential of chronotherapy are taken into account and leveraged to the greatest extent possible.…”

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

“…This breach allows inflammatory factors from the bloodstream and peripheral immune cells to infiltrate the brain parenchyma, exacerbating neuroinflammation and eventual cell death within the brain parenchyma. Abbreviations: Fpn, ferroportin; FtMt, ferritin mitochondrial; MMP2, matrix Metallopeptidase Understanding the molecular mechanisms underlying blood-brain barrier damage and its consequences on the central nervous system is crucial due to the heavy reliance of the central nervous system on the physiological state of the neurovascular unit (NVU) in the brain [188]. Ferroptosis and neuroinflammation have emerged as significant mechanisms implicated in the progression and outcomes of blood-brain barrier injury during disease processes [189].…”