A simulation of recreational and addictive methamphetamine use on theintegrity of the blood-brain barrier endothelium using an in vitro BBBmodel

Abstract

Methamphetamine (Meth) is a widely abused psychostimulant implicated in severeneuropathologies, such as hemorrhagic stroke, which arises from disruptions to theblood-brain barrier (BBB). The selectively permeable BBB, composed primarily of brainmicrovascular endothelial cells (BMVECs) forms the cerebral capillaries and serves as thebrain’s protective interface against circulating toxins and pathogens. Despite its recog-nized susceptibility to Meth, the direct effects of Meth exposure on BMVECs remaininsufficiently understood. To model the two types of Meth users, recreational andaddictive, bEnd.5 cells were exposed to Meth for 24 hours only or daily. Changes incellular division, mitochondrial activity, cellular morphology, and barrier integrity wereassessed using the trypan blue exclusion assay, XTT, Hematoxylin and Eosin (H&E) stain,and transendothelial electrical resistance (TEER), respectively. Acute Meth exposuresuppressed cellular division and reduced Mitochondrial activity (MA) in a 24-houroscillatory manner, while chronic Meth exposure induced a sustained suppression ofcellular division. Morphological analyses revealed nuclear abnormalities consistent withmitotic disruption. Both exposure conditions reduced endothelial monolayer integrityover the 96-hours; however, chronic exposure caused exacerbated decreases in barrierintegrity. Notably, even acute Meth exposure was sufficient to initiate long-term BBBendothelium dysfunction. These findings demonstrate a continuum of BBB vulnerabilityarising from both recreational and addictive Meth use, underscoring the critical need forearly intervention to avert progressive cerebrovascular, hemorrhagic, and neurologicaldamage.