Neurovascular Unit Dysfunction and Blood–Brain Barrier Hyperpermeability Contribute to Schizophrenia Neurobiology: A Theoretical Integration of Clinical and Experimental Evidence

Frontiers in Psychiatry

Derek Chong¹  Amanda Najjar²  Virginia De Sanctis³  Silky Pahlajani³  Souhel Najjar³  Joel N. H. Stern³ 

[1] Department of Neurology, Hofstra Northwell School of Medicine, New York, NY, USA;Department of Psychology and Human Development, Peabody College, Vanderbilt University, Nashville, TN, USA;Neuroinflammation Division, Department of Neurology, Lenox Hill Hospital, New York, NY, USA;

关键词: schizophrenia;    blood–brain barrier;    neurovascular unit;    endothelial cell;    neuroinflammation;    oxidative stress;   

DOI  :  10.3389/fpsyt.2017.00083

来源: DOAJ

【 摘 要 】

Schizophrenia is a psychotic disorder characterized by delusions, hallucinations, negative symptoms, as well as behavioral and cognitive dysfunction. It is a pathoetiologically heterogeneous disorder involving complex interrelated mechanisms that include oxidative stress and neuroinflammation. Neurovascular endothelial dysfunction and blood–brain barrier (BBB) hyperpermeability are established mechanisms in neurological disorders with comorbid psychiatric symptoms such as epilepsy, traumatic brain injury, and Alzheimer’s disease. Schizophrenia is frequently comorbid with medical conditions associated with peripheral vascular endothelial dysfunction, such as metabolic syndrome, cardiovascular disease, and diabetes mellitus. However, the existence and etiological relevance of neurovascular endothelial dysfunction and BBB hyperpermeability in schizophrenia are still not well recognized. Here, we review the growing clinical and experimental evidence, indicating that neurovascular endotheliopathy and BBB hyperpermeability occur in schizophrenia patients. We present a theoretical integration of human and animal data linking oxidative stress and neuroinflammation to neurovascular endotheliopathy and BBB breakdown in schizophrenia. These abnormalities may contribute to the cognitive and behavioral symptoms of schizophrenia via several mechanisms involving reduced cerebral perfusion and impaired homeostatic processes of cerebral microenvironment. Furthermore, BBB disruption can facilitate interactions between brain innate and peripheral adaptive immunity, thereby perpetuating harmful neuroimmune signals and toxic neuroinflammatory responses, which can also contribute to the symptoms of schizophrenia. Taken together, these findings support the “mild encephalitis” hypothesis of schizophrenia. If neurovascular abnormalities prove to be etiologically relevant to the neurobiology of schizophrenia, then targeting these abnormalities may represent a promising therapeutic strategy.

【 授权许可】

Unknown