Vascular Endothelium Is a Site of Free Radical Production and Inflammation in Areas of Neuronal Loss in Thiamine‐deficient Brain

Free radical production in vascular endothelial cells and inflammatory responses in perivascular microglia accompany the selective neuronal death induced by TD. Lipid peroxidation and tyrosine nitration occur in neurons within susceptible areas. Thus, region- and cell-specific oxidative stress contributes to selective neurodegeneration during TD. These data are consistent with the hypothesis that in TD, vascular factors constitute a critical part of a cascade of events leading to increases in blood-brain barrier permeability to nonneuronal proteins and iron, leading to inflammation and oxidative stress. Inflammatory cells may release deleterious compounds or cytokines that exacerbate the oxidative damage to metabolically compromised neurons. Similar mechanisms may operate in the pathophysiology of neurodegenerative diseases in which vascular factors, inflammation and oxidative stress are implicated including AD.