Magnesium in a Polyethylene Glycol Formulation Provides Neuroprotection After Unilateral Cervical Spinal Cord Injury

Abstract

MgCl₂ in a PEG formulation reduced secondary damage and improved behavioral recovery when administered 2 hours after a unilateral cervical hemicontusion injury. These findings are consistent with the neurologic benefit observed when administering this magnesium formulation in contusive and compressive models of thoracic SCI. Demonstrating the robustness of this neuroprotective effect in multiple injury models (and in the cervical injury model in particular) is important when considering the applicability of such a therapy for human SCIs.

Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats

“…injections of magnesium improved lesion volume, although not locomotor function, following contusive SCI. 18,30 Our study is also in apparent contrast to the finding that two i.v. injections of magnesium within the first 6 h result in dorsal white matter sparing and a small improvement in locomotor function in rats with a compression injury.…”

“…15,16 Our dosing is in the range that is deemed tolerable in humans. 18,30 Our data show that MgCl 2 can improve microvascular perfusion after a contusive SCI. The extent of maintained perfusion was similar with 24 or 48 h infusions.…”

“…One such possible combination of vasodilator and endothelial protective agent might have been present in the combination of magnesium and polyethylene glycol. 18,30 The latter is a synthetic polymer, and reportedly has neuroprotective effects in acute SCI. 17,76,77 Its effects might be mediated by its ability to fuse cell membranes and this may include endothelial cells.…”

The Evaluation of Magnesium Chloride within a Polyethylene Glycol Formulation in a Porcine Model of Acute Spinal Cord Injury

“…It was developed as a therapeutic intervention for acute spinal cord injury (SCI) and was subsequently reported to be neuroprotective in compressive and contusive models of thoracic and cervical SCI in the rat. 11,18,19 Treating animals with AC105 decreased lesion volumes by 67%, and open field locomotion (Basso, Beattie, Bresnahan) scores were significantly improved compared to a saline-treated group (10.0 -0.2 vs. 7.8 -0.4). 19 Importantly, the doses of magnesium in the AC105 formulation (5 infusions of 190 lmol/kg) used in the rodent thoracic and cervical SCI model by Kwon and colleagues 19 and Lee and colleagues, 18 respectively, were within the range of human tolerability and comparable to doses that previously have appeared to be safe in clinical trials of stroke and cardiac arrest (4 g of bolus within 12 h post-injury, followed by 16 g over 24 h).…”

“…11,18,19 Treating animals with AC105 decreased lesion volumes by 67%, and open field locomotion (Basso, Beattie, Bresnahan) scores were significantly improved compared to a saline-treated group (10.0 -0.2 vs. 7.8 -0.4). 19 Importantly, the doses of magnesium in the AC105 formulation (5 infusions of 190 lmol/kg) used in the rodent thoracic and cervical SCI model by Kwon and colleagues 19 and Lee and colleagues, 18 respectively, were within the range of human tolerability and comparable to doses that previously have appeared to be safe in clinical trials of stroke and cardiac arrest (4 g of bolus within 12 h post-injury, followed by 16 g over 24 h). [20][21][22][23][24][25] A comparison between MgSO 4 -PEG and MgCl 2 -PEG showed no statistical difference between the two salts, but the investigators noted that the AC105-treated group appeared to have slightly better locomotor recovery early post-SCI.…”