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J Cereb Blood Flow Metab. 2016 Mar;36(3):539-54. doi: 10.1177/0271678X15616978. Epub 2015 Nov 17.

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress.

Author information

1
Center for Blood-Brain Barrier Research, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
2
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD, USA.
3
Center for Blood-Brain Barrier Research, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, USA luca.cucullo@ttuhsc.edu.

Abstract

Psychostimulants and nicotine are the most widely abused drugs with a detrimental impact on public health globally. While the long-term neurobehavioral deficits and synaptic perturbations are well documented with chronic use of methamphetamine, cocaine, and nicotine, emerging human and experimental studies also suggest an increasing incidence of neurovascular complications associated with drug abuse. Short- or long-term administration of psychostimulants or nicotine is known to disrupt blood-brain barrier (BBB) integrity/function, thus leading to an increased risk of brain edema and neuroinflammation. Various pathophysiological mechanisms have been proposed to underlie drug abuse-induced BBB dysfunction suggesting a central and unifying role for oxidative stress in BBB endothelium and perivascular cells. This review discusses drug-specific effects of methamphetamine, cocaine, and tobacco smoking on brain microvascular crisis and provides critical assessment of oxidative stress-dependent molecular pathways focal to the global compromise of BBB. Additionally, given the increased risk of human immunodeficiency virus (HIV) encephalitis in drug abusers, we have summarized the synergistic pathological impact of psychostimulants and HIV infection on BBB integrity with an emphasis on unifying role of endothelial oxidative stress. This mechanistic framework would guide further investigations on specific molecular pathways to accelerate therapeutic approaches for the prevention of neurovascular deficits by drugs of abuse.

KEYWORDS:

Drug abuse; alternative; blood-brain barrier; cocaine; methamphetamine; nicotine; oxidative stress; tight junctions

PMID:
26661236
PMCID:
PMC4794105
[Available on 2017-03-01]
DOI:
10.1177/0271678X15616978
[Indexed for MEDLINE]
Free PMC Article

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