Blood brain barrier: Fluid Transfer

Basic, Clinical - Neurologic, Organ-Based and Clinical Sciences

The blood brain barrier (BBB) is a specialized barrier that renders the environment of the central nervous system (CNS) separate from other compartments of the body. The unique environment provided by the BBB enables the specialized activity of neurons; BBB breakdown is the result of pathologic conditions and leads to further neuronal dysfunction. The unique requirements of the CNS require the BBB to limit the free exchange of some solutes that would be freely exchanged through other anatomic compartments. The restriction of solute transport limits how fluids can transfer across the BBB.

BBB disruption is mediated by a number of soluble factors which are associated with diverse pathologic conditions, these include : glutamate, endothelin-1, NO, MIP-2, TNFα, MIP2, bradykinin, histamine, and free radicals among others.5 Hypoxic and ischemic insults lead to disruption of TJ by events set in motion by VEGF, NO, and various cytokines. VEGF expression induces fenestration in unfenestrated endothelial cells in the BBB.6 Sepsis can mediate BBB disruption via perivascular edema and astrocyte end-foot edema, rupture, and detachment.7 The BBB in the area surrounding a brain tumor is poorly developed. This is the result of failure to express critical TJ proteins. In glioblastoma, claudin-1 is found to be absent and claudin-5 and occludin significantly downregulated.8 Similar events occur in astrocytoma and metastatic adenocarcinoma leading to improperly formed TJ.9 The consequence of these events is the increased permeability to a variety of (potentially neurotoxic) solutes, and cerebral edema. AQP4 is significantly upregulated in several forms of brain tumor contributing to water influx and disruption of delicate neural homeostasis.10 Edema caused by disruption of the BBB leads to brain swelling and potentially life threatening increases in intracranial pressure (ICP).

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