Astrocyte dysfunction and neurovascular impairment in neurological disorders: Correlation or causation?

• Published in: Neurochemistry international Vol. 128; pp. 70 - 84
• Main Authors: McConnell, Heather L., Li, Zhenzhou, Woltjer, Randall L., Mishra, Anusha
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2019
• Subjects: Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Astrogliosis; Blood-brain barrier; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Brain - metabolism; Brain - pathology; Gliosis - metabolism; Gliosis - pathology; Humans; Nervous System Diseases - metabolism; Nervous System Diseases - pathology; Neurodegeneration; Neurovascular coupling; Neurovascular Coupling - physiology; Neurovascular unit; BBB; CBF; NVU; LPS; Astrogliosis; ARTAG; Blood-brain barrier; Neurodegeneration; CSD; TBI; IF; Neurovascular coupling; EETs; 20-HETE; PGE2; AD; Astrocytes; FTLD; DCI; GFAP; TGFβ1; CTE; NVC; Neurovascular unit; SAH
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2019.04.005

The neurovascular unit, consisting of neurons, astrocytes, and vascular cells, has become the focus of much discussion in the last two decades and emerging literature now suggests an association between neurovascular dysfunction and neurological disorders. In this review, we synthesize the known and suspected contributions of astrocytes to neurovascular dysfunction in disease. Throughout the brain, astrocytes are centrally positioned to dynamically mediate interactions between neurons and the cerebral vasculature, and play key roles in blood-brain barrier maintenance and neurovascular coupling. It is increasingly apparent that the changes in astrocytes in response to a variety of insults to brain tissue –collectively referred to as “reactive astrogliosis” – are not just an epiphenomenon restricted to morphological alterations, but comprise functional changes in astrocytes that contribute to the phenotype of neurological diseases with both beneficial and detrimental effects. In the context of the neurovascular unit, astrocyte dysfunction accompanies, and may contribute to, blood-brain barrier impairment and neurovascular dysregulation, highlighting the need to determine the exact nature of the relationship between astrocyte dysfunction and neurovascular impairments. Targeting astrocytes may represent a new strategy in combinatorial therapeutics for preventing the mismatch of energy supply and demand that often accompanies neurological disorders.
•Astrocytes are centrally positioned to regulate the blood-brain barrier, cerebral blood flow, and neurovascular coupling•In reactive astrogliosis, astrocyte mediation of these processes may be impaired.•Astrocyte dysfunction and the resultant cerebrovascular impairments may be a primary contributor to neuronal dysfunction.•Therapies that protect neurons in isolation while ignoring their glial and vascular context may be intrinsically limited.