Intravenous infusion of magnesium reduced potentially neurotoxic glutamate levels. - GreenMedInfo Summary
AC105 Increases Extracellular Magnesium Delivery and Reduces Excitotoxic Glutamate Exposure within Injured Spinal Cords in Rats.
J Neurotrauma. 2016 Aug 8. Epub 2016 Aug 8. PMID: 27503053
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 by 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 to that of MgSO4alone. 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 singleivinfusion of saline or of MgSO4at 192µmol/kg did not significantly change extracellular Mg2+concentrations. However, a single infusion of AC105 (a MgCl2in PEG) at an equimolar Mg2+dose significantly increased the Mg2+concentration to 0.3 mM (core area) and 0.25 mM (rostral peri-lesion area). Moreover, multiple AC105 treatments completely restored the depleted extracellular Mg2+concentrations after SCI to levels in the uninjured spinal cord. Repeated MgSO4infusions slightly increased the Mg2+concentrations while saline infusion had no effect. In addition, AC105 treatment significantly reduced extracellular glutamate levels in the lesion center after SCI. These results indicate that intravenous infusion of PEG-formulated Mg2+normalized the Mg2+homeostasis following SCI and reduced potentially neurotoxic glutamate levels, consistent with a neuroprotective mechanism of blocking excitotoxicity.