ICAM-1 expression corresponds with perivascular cuffing, fibrinogen leakage, and the presence of VEEV in the brains of VEEV infected mice. (a) H&E staining of the brain of VEEV infected CD-1 mice exhibited prominent perivascular cuffs throughout the brain. (b) Endothelial cells are hypertrophied and exhibit positive immunoreactivity for ICAM-1. (c) Immunohistochemistry for fibrinogen demonstrated localized fibrinogen leakage around hypertrophied endothelial cells, indicating disruption of the BBB. (d) Extensive VEEV specific staining revealed numerous cells infected with VEEV around the affected vessels. (e) Perivascular cuffs were composed of moderate numbers of mononuclear cells, primarily lymphocytes and fewer monocytes which had transmigrated the endothelium and multifocally extended into the neuropil. (f) Neurons were primarily infected with VEEV; however, VEEV antigen was also localized in glia and fewer lymphocytes. (g) Vacuolation of the neuropil was observed around the affected vessels.