Microglia-Endothelium Interaction during Developmentĭuring embryogenesis, the formation of the BBB is a gradual process that starts with sprouting and invagination of newly formed branches from the perineural vascular plexus through angiogenesis ( Ruhrberg and Bautch, 2013). In this review, we discuss current concepts underlying the interactions between the vascular system and glial cells, in particular, the microglia-the CNS resident macrophages-in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative diseases. The neurovascular unit (NVU) is at the basis of neurovascular coupling, which allows cerebral blood flow to be locally regulated according to neuronal activity in specific areas of the brain, contributing to normal CNS functioning ( Zlokovic, 2008). Brain ECs are closely associated and functionally assembled in what is termed the “neurovascular unit”, composed by ECs, neurons, pericytes and glia ( Iadecola, 2004).

They act as a selective physical barrier known as the blood brain barrier (BBB), a unique specialized structure of the central nervous system (CNS) capillary bed based on EC tight junctions, with no endothelial fenestrae, and expression of specific membrane transporters, thus ensuring homeostasis and proper functioning of the brain. Brain endothelial cells (ECs) are especially suited for these functions. Moreover, it has a vital function in maintaining a stable ionic environment and protecting against neurotoxic substances critical for normal brain development and function. The cerebrovasculature plays a crucial role in oxygen and nutrient delivery to the organ with the highest metabolic demand in the body, the brain. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. On the other hand, the endothelium can regulate the state of microglial activation. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function.

In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. The crosstalk between these cells guarantees a proper environment for brain function. The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU).

Laboratório de Morfogênese Celular, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Bloco F, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Anna Carolina Carvalho da Fonseca Diana Matias Celina Garcia Rackele Amaral Luiz Henrique Geraldo Catarina Freitas Flavia Regina Souza Lima*

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