Fig. 8

BBB instability, pericyte thickness, and ZO1 loss correlate with the severity of SIVE. The severity of encephalitis was approximated by counting the average number of lesions per square cm of white matter tissue (n = 15 slides per SIVE animal). Each point on the graph designates the mean value of one SIVE animal (a–c). ZO1 MPI decreased in accordance with the lesion number (p < 0.05, r² = 0.689) (a). The average pericyte area increases with lesion number (p < 0.01, r² = 0.842) (b). The percent of vessels demonstrating fibrinogen extravasation increased with lesion number (p < 0.05, r² = 0.716) (c). Lines demonstrate linear regressions (a–c). An illustrative representation of changes with the glio-vascular unit through disease progression depicts a section of the BBB in uninfected, SIV-infected, and SIVE animals (d). Uninfected animals have an intact endothelium with TJPs between endothelial cells, non-hypertrophied pericytes, fibrinogen confined within the lumen of brain vessels, Shh localized primarily in the open space pace between the endothelial cells and the astrocyte endfeet (d), left panel. SIV-infected animals show a partially fenestrated endothelium missing some TJPs, hypertrophied pericytes with increased netrin-1, some fibrinogen escaping the lumen, and Shh more heavily localized to the endothelium (d), middle panel. Within the lesion, encephalitic animals have a highly fenestrated endothelial layer with an almost complete loss of TJPs, high levels of fibrinogen extravasation, a complete loss of pericytes and netrin-1, and a high proportion of Shh localized to the endothelium (d), right panel