Ca²⁺ homeostasis in brain microvascular endothelial cells

Blood brain barrier (BBB) is formed by the brain microvascular endothelial cells (BMVECs) lining the wall of brain capillaries. Its integrity is regulated by multiple mechanisms, including up/downregulation of tight junction proteins or adhesion molecules, altered Ca²⁺ homeostasis, remodeling of cytoskeleton, that are confined at the level of BMVECs. Beside the contribution of BMVECs to BBB permeability changes, other cells, such as pericytes, astrocytes, microglia, leukocytes or neurons, etc. are also exerting direct or indirect modulatory effects on BBB. Alterations in BBB integrity play a key role in multiple brain pathologies, including neurological (e.g. epilepsy) and neurodegenerative disorders (e.g. Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis etc.). In this review, the principal Ca²⁺ signaling pathways in brain microvascular endothelial cells are discussed and their contribution to BBB integrity is emphasized. Improving the knowledge of Ca²⁺ homeostasis alterations in BMVECa is fundamental to identify new possible drug targets that diminish/prevent BBB permeabilization in neurological and neurodegenerative disorders.