Abstract P161: Angiotensin Receptor Blockade Decreases Glutamate-induced Brain Inflammation
Chronic Kidney Disease (CKD) is very frequently associated with brain inflammation and cell injury leading to cognitive loss. At present a combined treatment of related kidney and brain injury has never been proposed. We focused on glutamate-induced excitotoxicity and neuronal inflammation, and on the effects of candesartan, a renoprotective Angiotensin Receptor Blocker (ARB) ameliorating hypertension and diabetes-induced kidney damage, and with accompanying neuroprotective efficacy. Primary cerebellar granule cells (CGC) were exposed to 100 μM glutamate and pre-treated for one hour with candesartan at neuroprotective concentrations (10 μM). Gene expression was quantified by qPCR. Candesartan significantly reduced glutamate-induced inflammation. Multiple group comparisons were performed by one-way ANOVA followed by Newman-Keuls post-test. Exposure to glutamate significantly reduced neuronal viability while up-regulating the expression of multiple genes on pro-inflammatory pathways, including Toll-like receptor 7 (Tlr7) and Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, p49/p100 (Nfkpb2). * p<0.01, ** p< 0.05, vs control; # p< 0.01 vs glutamate. In all cases, pretreatment with candesartan completely prevented glutamate-induced neurotoxicity. Our results indicate that Angiotensin II receptor blockade with candesartan is strongly and directly neuroprotective, significantly ameliorating neuronal injury as a result of glutamate excitotoxicity. These results support the use of candesartan and other ARBs for the concomitant treatment of CKD and associated neuronal injury.
Author Disclosures: J. Saavedra: None. A.G. Elkahloun: None. R. Hafko: None.
- © 2015 by American Heart Association, Inc.