blood glutamate scavenging insight into neuroprotection血液中谷氨酸清除了解神经保护.pdf

Int. J. Mol. Sci. 2012, 13, 10041-10066; doi:10.3390/ijms130810041 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Blood Glutamate Scavenging: Insight into Neuroprotection Akiva Leibowitz †,*, Matthew Boyko †, Yoram Shapira and Alexander Zlotnik Department of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University, Beer Sheva 84894, Israel; E-Mails: mathewb@bgu.ac.il (M.B.); yoramsh@.il (Y.S.); zlotnika@bgu.ac.il (A.Z.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: akival@bgu.ac.il; Tel: +972-8-6400262; Fax: +972-8-6403795. Received: 4 June 2012; in revised form: 18 July 2012 / Accepted: 30 July 2012 / Published: 13 August 2012 Abstract: Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to