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

Ravi K. Sajja, Shafiqur Rahman, Luca Cucullo

Research output: Contribution to journalReview articlepeer-review

106 Scopus citations

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.

Original languageEnglish
Pages (from-to)539-554
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number3
DOIs
StatePublished - 1 Mar 2016
Externally publishedYes

Keywords

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

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