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AC105 Increases Extracellular Magnesium Delivery and Reduces Excitotoxic Glutamate Exposure within Injured Spinal Cords in Rats

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Abstract Magnesium (Mg2+) homeostasis is impaired following spinal cord injury (SCI) and the loss of extracellular Mg2+ contributes to secondary injury by various mechanisms, including glutamate neurotoxicity. The neuroprotective effects… Click to show full abstract

Abstract Magnesium (Mg2+) homeostasis is impaired following spinal cord injury (SCI) and the loss of extracellular Mg2+ contributes to secondary injury by various mechanisms, including glutamate neurotoxicity. The neuroprotective effects of high dose Mg2+ supplementation have been reported in many animal models. Recent studies found that lower Mg2+ doses also improved neurologic outcomes when Mg2+ was formulated with polyethylene glycol (PEG), suggesting that a PEG/ Mg2+ formulation might increase Mg2+ delivery to the injured spinal cord, compared with that of MgSO4 alone. Here, we assessed spinal extracellular Mg2+ and glutamate levels following SCI in rats using microdialysis. Basal levels of extracellular Mg2+ (∼0.5 mM) were significantly reduced to 0.15 mM in the core and 0.12 mM in the rostral peri-lesion area after SCI. A single intravenous infusion of saline or of MgSO4 at 192 μmoL/kg did not significantly change extracellular Mg2+ concentrations. However, a single infusion of AC105 (a MgCl2 in PEG...

Keywords: injured spinal; delivery; magnesium; mg2; extracellular mg2; glutamate

Journal Title: Journal of Neurotrauma
Year Published: 2017

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