Cellular mechanisms and molecular signaling pathways in stress-induced anxiety, depression, and blood-brain barrier inflammation and leakage.

Depression and anxiety are comorbid conditions in many neurological or psychopathological disorders. Stress is an underlying event that triggers development of anxiety and depressive-like behaviors. Recent experimental data indicate that anxiety and depressive-like behaviors occurring as a result of stressful situations can cause blood-brain barrier (BBB) dysfunction, which is characterized by inflammation and leakage. However, the underlying mechanisms are not completely understood. This paper sought to review recent experimental preclinical and clinical data that suggest possible molecular mechanisms involved in development of stress-induced anxiety and depression with associated BBB inflammation and leakage. Critical therapeutic targets and potential pharmacological candidates for treatment of stress-induced anxiety and depression with associated BBB dysfunctions are also discussed.