PT - JOURNAL ARTICLE AU - Therese S. Salameh AU - Gul N. Shah AU - Tulin O. Price AU - Melvin R. Hayden AU - William A. Banks TI - Blood–Brain Barrier Disruption and Neurovascular Unit Dysfunction in Diabetic Mice: Protection with the Mitochondrial Carbonic Anhydrase Inhibitor Topiramate AID - 10.1124/jpet.116.237057 DP - 2016 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 452--459 VI - 359 IP - 3 4099 - http://jpet.aspetjournals.org/content/359/3/452.short 4100 - http://jpet.aspetjournals.org/content/359/3/452.full SO - J Pharmacol Exp Ther2016 Dec 01; 359 AB - All forms of diabetes mellitus are characterized by chronic hyperglycemia, resulting in the development of a number of microvascular and macrovascular pathologies. Diabetes is also associated with changes in brain microvasculature, leading to dysfunction and ultimately disruption of the blood–brain barrier (BBB). These changes are correlated with a decline in cognitive function. In diabetes, BBB damage is associated with increased oxidative stress and reactive oxygen species. This occurs because of the increased oxidative metabolism of glucose caused by hyperglycemia. Decreasing the production of bicarbonate with the use of a mitochondrial carbonic anhydrase inhibitor (mCAi) limits oxidative metabolism and the production of reactive oxygen species. In this study, we have demonstrated that 1) streptozotocin-induced diabetes resulted in BBB disruption, 2) ultrastructural studies showed a breakdown of the BBB and changes to the neurovascular unit (NVU), including a loss of brain pericytes and retraction of astrocytes, the two cell types that maintain the BBB, and 3) treatment with topiramate, a mCAi, attenuated the effects of diabetes on BBB disruption and ultrastructural changes in the neurovascular unit.