PMC:7463108 / 53449-55481 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7463108","sourcedb":"PMC","sourceid":"7463108","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7463108","text":"Despite growing evidence on how opiates and HIV interact to impact the neuropathology of HIV, little is known about their interactive effects on the blood-brain barrier (BBB). BBB integrity and function are critical for maintaining CNS homeostasis, and mediating neuroimmune interactions with the periphery and drug delivery into the CNS. HIV and many individual HIV proteins can breakdown the BBB disrupting tight junction proteins (Dallasta et al. 1999; Boven et al. 2000; Andras et al. 2003; Mahajan et al. 2008; Banerjee et al. 2010; Gandhi et al. 2010; Xu et al. 2012; Patel et al. 2017) and decreasing transendothelial electrical resistance (TEER) (an in vitro measure of barrier integrity) (Mahajan et al. 2008; Gandhi et al. 2010; Mishra and Singh 2014; Patel et al. 2017), with resultant paracellular “leakage” of compounds/current between compromised barrier endothelial cells (Mahajan et al. 2008; Gandhi et al. 2010; Wen et al. 2011; McLane et al. 2014; Leibrand et al. 2017, 2019). Although opioids can also impair the BBB through alterations in tight junction proteins and/or increased paracellular flux (Baba et al. 1988; Mahajan et al. 2008; Wen et al. 2011; Leibrand et al. 2019), others have found that it is morphine withdrawal, not the continued exposure to morphine, that most greatly disrupts BBB integrity (Sharma and Ali 2006). In addition to perturbing paracellular dynamics, morphine may also alter the expression and/or function of drug efflux proteins, such as P-glycoprotein (P-gp). Sub-chronic and chronic morphine exposure is reported to increase P-gp expression and/or function (Aquilante et al. 2000; Mahajan et al. 2008; Yousif et al. 2008; Leibrand et al. 2019). Alternatively, other investigators report no changes in P-gp with chronic exposure (Chaves et al. 2016), while some see increases upon morphine withdrawal (Yousif et al. 2012; Chaves et al. 2016). Alterations in drug transport proteins would impact the central accumulation and efficacy of therapeutic drugs that are their 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