Abstract
One of the hallmark features underlying the pathogenesis of HIV encephalitis is the disruption of blood–brain barrier (BBB). Cocaine, often abused by HIV-infected patients, has been suggested to worsen the HIV-associated dementia (HAD) via unknown mechanisms. The objective of the present study was to explore the effects of cocaine on BBB permeability using human brain microvascular endothelial cells (HBMECs). Additionally, because the chemokine CCL2 and its receptor CCR2 play a crucial role in the recruitment of inflammatory cells into the central nervous system in HAD brains, we tested for the effect of cocaine in modulating the CCL2/CCR2 axis. Our findings suggest that exposure of HBMECs to cocaine correlated with the breakdown of ZO-1 tight junction protein and reorganization of the cytoskeleton resulting in stress fiber formation. Furthermore, cocaine also modulated upregulation of the CCL2/CCR2 axis in monocytes. These findings conform to the multifaceted effects of cocaine leading to accelerated progression of HIV-1 neuropathogenesis.
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Acknowledgements
We gratefully acknowledge the technical assistance of Fenglan Jia for cell culture studies.
This work was supported by grant DA020392-01 and RR016443 from the National Institutes of Health.
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Dhillon, N.K., Peng, F., Bokhari, S. et al. Cocaine-mediated Alteration in Tight Junction Protein Expression and Modulation of CCL2/CCR2 Axis Across the Blood-Brain Barrier: Implications for HIV-Dementia. J Neuroimmune Pharmacol 3, 52–56 (2008). https://doi.org/10.1007/s11481-007-9091-1
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DOI: https://doi.org/10.1007/s11481-007-9091-1