Vascular Presence of HHV-6 in Substantia Nigra Pars Compacta of Chronic Alcohol Users and Controls: A Histopathological Evaluation

Objectives. Human herpesvirus-6 (HHV-6) is a double-stranded herpesvirus that has a tropism for endothelial cells, particularly in organs such as the brain and liver. Despite uncertainties about its exact pathogenesis, recent research suggests a connection between the virus and a number of central nervous system disorders. We hypothesized that the virus and chronic alcohol abuse may act synergistically to alter the blood-brain barrier, given the virus's known propensity for hematogenous spread. Herein, we investigated the presence of HHV-6 proteins in endothelial cells of gray (GM) and white matter (WM) within the dopaminergic-neuron-rich region of the Substantia Nigra pars compacta (SNpc).

Methods. 18 brain autopsy specimens with a history of chronic alcohol use were compared with 13 young non-alcohol users (controls). 10 visual fields per region in each slide were evaluated by light microscopy (40×) and quantitative estimation of HHV- 6 expression in vascular bed was performed. Results were analyzed using SPSS version 29.

Results. The median number of HHV-6+ vessels per vision field in GM and WM were three and five vessels, respectively. This difference in the distribution of HHV-6+ vessels between GM and WM was statistically significant (Wilcoxon signed rank test; P < 0.001). In WM, there were significant differences in distribution of HHV-6+ vessels between controls and chronic alcohol users (Mann-Whitney U; P < 0.001). Similar results were obtained in GM of SNpc.

Conclusions. Our results indicate the potential involvement of endothelium (especially in the WM) in the transmission of the virus from the periphery to the subcortical and basal ganglia regions through a modified blood-brain barrier in the background of chronic alcohol abuse.