HIV Tat Protein Increases Blood‐Brain Barrier Permeability: In Vitro and In Vivo Evidence

Tat protein is synthesized and released by HIV infected cells into the extracellular space. The current study is based on the hypothesis that circulatory Tat can increase permeability of the blood‐brain barrier (BBB). Carotid surgeries were performed on C57BL/6 mice under anesthesia. The common carotid artery, external carotid artery (ECA), and internal carotid artery (ICA) were isolated. The ECA was ligated with 6–0 silk suture distal from the ICA and cut distal from ligated point. A catheter was introduced into this incision and advanced into the ICA. Tat and control substances were injected into the ICA and allowed to circulate for up to 24 h. As the marker of the BBB permeability, mice received sodium fluorescence (Na‐F) injection through the same catheter. Five minutes following Na‐F administration, the brains were perfused and harvested. The permeability index was assayed as Na‐F brain/plasma content. Furthermore, expression of tight junction proteins was evaluated following Tat exposure in the brain tissues and cultured brain microvascular endothelial cells. Tat protein markedly increased the BBB permeability and decreased tight junction protein expression. These results provide additional evidence that Tat can play an important role in HIV‐1 trafficking into the brain, the event that precedes the development of HIV‐1‐associated encephalopathy. Supported by MH63022, MH072567, and NS39254.