title: Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?
abstract: The blood-brain barrier (BBB) regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS) in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer's disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD), here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species) substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.
authors.affiliation: MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada L8S 4L8.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Patel
authors.affiliation: MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada L8S 4L8 ; Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, ON, Canada L8P 3B6 ; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada L8S 4L8.
authors.forename: Benicio N
authors.initials: BN
authors.lastname: Frey
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000209:etiology / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D004660:Encephalitis / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008959:Models, Neurological; D018384:Oxidative Stress
chemical_list: D018836:Inflammation Mediators; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9