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Amiloride is neuroprotective in an MPTP model of Parkinson’s disease. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. Archives of Internal Medicine, 164(13), 1422–1426.Īlvarez de la Rosa, D., Krueger, S.

The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: A population-based study of 13,000 men and women with 20 years of follow-up. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Understanding the pathways mediating exacerbated ischemic brain injury in RH-exposed ITD rats may help lower diabetic aggravation of ischemic brain damage.ĪDA Workgroup on Hypoglycemia. The results show the role of ASIC in post-ischemic hypoperfusion and increased ischemic damage in RH-exposed ITD rats. We observed that SOCE in VSMCs at lower pH is ASIC3 dependent. Since ASIC activation-induced store-operated calcium entry (SOCE) plays a role in vascular tone, next we tested if acidosis activates SOCE via activating ASICs in vascular smooth muscle cells (VSMCs). Inhibition of ASICs prevented RH-induced increase in the extent of post-ischemic hypoperfusion and ischemic brain injury. Post-ischemic hypoperfusion in RH-exposed rats was of greater extent than that in control rats. Ischemic brain injury in hippocampus was evaluated using histopathology. Cerebral blood flow was measured using laser Doppler flowmetry. Transient global cerebral ischemia was induced overnight after RH. ITD rats were exposed to RH for 5 days and were randomized into Psalmotoxin1 (PcTx1, ASIC1a inhibitor), APETx2 (ASIC3 inhibitor), or vehicle groups. Streptozotocin-diabetic rats treated with insulin were considered ITD rats.

The present study evaluated the hypothesis that increased intra-ischemic acidosis in RH-exposed ITD rats leads to pronounced post-ischemic hypoperfusion via activation of acid-sensing (proton-gated) ion channels (ASICs). We showed previously that RH exposure increases ischemic brain damage in insulin-treated diabetic (ITD) rats.

Anti-diabetic therapy mitigates this complication but increases the risk of exposure to recurrent hypoglycemia (RH). Diabetes is a chronic metabolic disease and cerebral ischemia is a serious complication of diabetes.