Neuropathological alterations in drug abusers: The involvement of neurons, glial, and vascular systems

Because the effects of drug abuse on the cellular elements of the human brain have not been studied systematically, an investigation was performed using histology, immunohistochemistry, and morphometry. The main cortical and subcortical brain areas of 50 polydrug deaths were analyzed as compared with controls. In the brains of drug abusers, a significant neuronal loss was present. Interestingly, the number of glial fibrillary acidic protein (GFAP)-positive astrocytes was reduced. the numerical density of perivascular and parenchymal microglia was increased in the white matter and in most subcortical regions. In the white matter there were widespread β-amyloid precursor protein deposits. Furthermore, there was a prominent vascular hyalinosis, endothelial cell proliferation, and a loss of immunoreactivity for collagen type IV within the vascular basal lamina. The neuronal loss seems to be the result of a direct impairment of nerve cells and, indirectly, to a damage of astrocytes, axons, and the microvasculature. The reduction of GFAP-positive astrocytes is also indicative of a drug-induced damage. The axonal injury suggests a toxic-metabolic drug effect, whereas the concomitant activation of microglia is indicative of a long-standing progressive process. The noninflammatory vasculopathy can be considered as the morphological substrate of a disturbed blood-brain barrier. Our findings demonstrate that drugs of abuse initiate a cascade of interacting toxic, vascular, and hypoxic factors that finally result in widespread disturbances within the complex network of central nervous system cell-cell interactions.