Membrane transporters in traumatic brain injury: Pathological, pharmacotherapeutic, and developmental implications

Experimental Neurology
Fanuel T. HagosPhilip E. Empey

Abstract

Membrane transporters regulate the trafficking of endogenous and exogenous molecules across biological barriers and within the neurovascular unit. In traumatic brain injury (TBI), they moderate the dynamic movement of therapeutic drugs and injury mediators among neurons, endothelial cells and glial cells, thereby becoming important determinants of pathogenesis and effective pharmacotherapy after TBI. There are three ways transporters may impact outcomes in TBI. First, transporters likely play a key role in the clearance of injury mediators. Second, genetic association studies suggest transporters may be important in the transition of TBI from acute brain injury to a chronic neurological disease. Third, transporters dynamically control the brain penetration and efflux of many drugs and their distribution within and elimination from the brain, contributing to pharmacoresistance and possibly in some cases pharmacosensitivity. Understanding the nature of drugs or candidate drugs in development with respect to whether they are a transporter substrate or inhibitor is relevant to understand whether they distribute to their target in sufficient concentrations. Emerging data provide evidence of altered expression and function of transpo...Continue Reading

Citations

Oct 9, 2020·Future Medicinal Chemistry·Bikram KhadkaJong-Sup Bae
Feb 25, 2020·Experimental Neurology·Eric E Abrahamson, Milos D Ikonomovic

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