Blood-brain barrier’s interplay with peripheral and central inflammation as a pathophysiological mechanism of bipolar disorders

Abstract

Abstract Both blood-brain barrier (BBB) disruptions and elevated inflammation have been found in patients with bipolar disorder (BD). Consistent studies found increased inflammation markers and proinflammatory cytokines levels in the serum of patients with BD. Systemic inflammation can alter BBB integrity and increase its permeability resulting in a lower brain protection. Notably, BBB leakage can facilitate cytokines and activated immune cell access to the brain and cause neuroinflammation by locally activating glial cells. Activated glial cells further damage BBB integrity through cytokines secretion or reactive oxygen species production. Consistently, recent studies found an increased neuroinflammation in BD patients. By maintaining inflammation, BBB leakage is thought to act on various pathways involved in BD physiopathology, such as hypothalamic-pituitary-adrenal axis dysregulation, serotonin and melatonin regulation, and neural cell survival or neurogenesis.