Neuropathological Alterations in Drug Abusers: The Involvement of Neurons, Glial, and Vascular Systems

Abstract

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.

Methamphetamine Causes Degeneration of Dopamine Cell Bodies and Terminals of the Nigrostriatal Pathway Evidenced by Silver Staining

“…However, to date, there are no published reports of anatomical evidence of dopamine neuronal destruction in SNpc of human methamphetamine abusers. Some evidence of neurodegenerative changes exists: for example, a specific decrease in pigmented neurons in SN of human abusers, similar to that seen in PD patients (Büttner and Weis, 2006;Büttner, 2011). Moreover, the morphology of the SN (as measured by transcranial sonography) in individuals with a history of stimulant abuse, including methamphetamine, is abnormal, and is associated with reduced dopamine uptake in the striatum and increased risk for development of PD (Todd et al, 2013).…”

Review: The neuropathology of drug abuse

“…Within the hippocampus of heroin deaths, enhanced expression of glial fibrillary acidic protein (GFAP) by astrocytes and/or a proliferation of microglia have been found [84]. However, an increased GFAP expression could not be confirmed by other authors [23]. An increase in polysialic acid neural cell adhesion molecule positive hippocampal neurones and astrocytes is assumed to reflect an attempt to repair cell damage [94].…”

“…Although a broad spectrum of alterations affecting the CNS has been described in drug abusers [1,2,23], there is no specific change that is characteristic and little is known about the fundamental neuropathological alterations of the cellular elements of the human brain. Therefore, despite a large body of literature on animal models, the following review will focus on the relevant human CNS findings.…”

Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders

“…In the post-mortem brains, a significant decrease in astrocytic numbers and morphological fragmentation of astrocytes, probably indicative of degenerative changes, have been documented (Büttner and Weis, 2006; Miguel-Hidalgo, 2009). At the same time an increase in GFAP expression and astroglial reactivity was also described in human brain samples and in various animal models of drug abuse and addiction (Armstrong et al, 2004; Fattore et al, 2002; Oehmichen et al, 1996; Suarez et al, 2000; Weber et al, 2013).…”