Oral L-citrulline administration improves memory deficits following transient brain ischemia through cerebrovascular protection. – ScienceOpen
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      Oral L-citrulline administration improves memory deficits following transient brain ischemia through cerebrovascular protection.

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          Abstract

          L-citrulline (L-Cit) is known to increase nitric oxide (NO) production via the increase of L-arginine (L-Arg) concentration in the blood and improve endothelial dysfunction in cardiovascular diseases. However, little is known about the effects of L-Cit on cerebrovascular dysfunction. Here we showed that oral L-Cit administration prevents cerebrovascular injury following cerebral ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. After BCCAO ischemia, mice were treated with L-Cit (50, 75, or 100 mg/kg p.o.) for 10 days once a day. L-Cit administration not only prevented neuronal cell death but also prevented capillary loss in the hippocampal region following brain ischemia. The cerebrovascular protective effect of L-Cit was associated with the restoration of endothelial nitric oxide synthase (eNOS) expression in the hippocampus. In addition, we devised a novel protocol to analyze NOx(-) (NO(2-) and NO(3-)) productions following L-Arg infusion using in vivo microdialysis and revealed that decreased L-Arg-induced NOx(-) levels were improved in the hippocampus of BCCAO mice following repeated L-Cit administration. Finally, memory deficits following brain ischemia were improved by oral administration of L-Cit. In summary, L-Cit is a potential therapeutic agent that protects cerebrovascular injury and in turn prevents neuronal cell death. Thereby, oral L-Cit administration improves cognitive deficits following brain ischemia.

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          Author and article information

          Journal
          Brain Res.
          Brain research
          1872-6240
          0006-8993
          Jul 3 2013
          : 1520
          Affiliations
          [1 ] Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
          Article
          S0006-8993(13)00656-2
          10.1016/j.brainres.2013.05.011
          23685189
          12721b2f-8e92-47ea-9175-e161d9f46d0c
          Copyright © 2013 Elsevier B.V. All rights reserved.
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