Drug Abuse-Related Neuroinflammation in Human Postmortem Brains: An Immunohistochemical Approach

Abstract

Abstract The aim of the study was to investigate blood-brain barrier alterations, neuroinflammation, and glial responses in drug abusers. Five immunohistochemical markers (CD3, zonula occludens-1 [ZO-1], intracellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule [VCAM-1], and glial fibrillary acidic protein [GFAP]) were assessed on postmortem brain samples collected from drug abusers who died from acute intoxication of cocaine, heroin, or a combination of both, compared with controls. CD3 and ICAM-1 immunopositivity were significantly stronger in drug abusers than in controls. VCAM-1 immunopositivity was similar across drug abuser and control groups. In heroin abusers, significantly lower ZO-1 immunopositivity was observed relative to controls. GFAP positivity did not show significant differences between groups, but its distribution within the brain did differ. Both cocaine and heroin abuse promoted neuroinflammation, increasing expression of ICAM-1 and recruiting CD3+ lymphocytes. Heroin affected the molecular integrity of tight junctions, as reflected by reduced ZO-1 expression. The outcomes of the present study are, overall, consistent with prior available evidence, which is almost exclusively from studies conducted in vitro or in animal models. These findings provide important information about the downstream consequences of neuroinflammation in drug abusers and may help to inform the development of potential therapeutic targets.