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Blood Glutamate Scavenging: Insight into Neuroprotection
Department of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University, Beer Sheva 84894, Israel
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
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 be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.
Keywords: glutamate; scavenging; neuroprotection; brain ischemia; traumatic brain injury
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MDPI and ACS Style
Leibowitz, A.; Boyko, M.; Shapira, Y.; Zlotnik, A. Blood Glutamate Scavenging: Insight into Neuroprotection. Int. J. Mol. Sci. 2012, 13, 10041-10066.
Leibowitz A, Boyko M, Shapira Y, Zlotnik A. Blood Glutamate Scavenging: Insight into Neuroprotection. International Journal of Molecular Sciences. 2012; 13(8):10041-10066.
Leibowitz, Akiva; Boyko, Matthew; Shapira, Yoram; Zlotnik, Alexander. 2012. "Blood Glutamate Scavenging: Insight into Neuroprotection." Int. J. Mol. Sci. 13, no. 8: 10041-10066.