Single cell genomics for cellular phenotyping: applications in brain disorder

Abstract

Neurovascular unit (NVU) is an elaborated multicellular brain-vessel-blood interface supporting a controlled blood-brain communication through the selective-permeable blood-brain barrier (BBB) and an adequate neurovascular and neurometabolic coupling. Impairment of NVU during aging and neurologic disorders is accompanied by microvascular dysfunction, BBB opening, neurovascular uncoupling, and neuroinflammation, with deleterious effects on brain microenvironment and neuronal signaling. After stroke, neurons are usually lost in the infarct core and astrocytes become reactive and proliferative, dysregulating the balance between neuronal and non-neuronal cells of the NVU in the lesioned area. In this review, we present major cytological responses of the NVU to cerebral ischemia with an emphasis on the aged brain. Early responses of the neurovascular unit to chronic hypoxia include neutrophils infiltration, brain edema, blood vessel disintegration, astrocytes and endothelial cells proliferation as well as conversion of resident microglia to phagocytic microglia. Later responses include the confinement of the peri-infarcted region by a scar tissue composed mainly of reactive astrocytes and endothelial cells, and angiogenesis. However, the newly formed capillary network is disorganized and the blood vessels are leaky making a successful regeneration of the damaged area, unlikely.