Object. The goal of this study was to establish the therapeutic window during which delayed therapy with MgSO ₄ improves neurological motor outcome in rats that have suffered severe traumatic axonal brain injury.

Methods. Severe brain injury was induced in male Sprague—Dawley rats by using the impact—acceleration model of severe traumatic diffuse axonal brain injury. Injured animals were subsequently treated with MgSO ₄ (750 µmol/kg) infused intramuscularly at 30 minutes or at 8, 12, or 24 hours after trauma and were tested for neurological motor outcome during the following week by using the rotarod test. Injured untreated (control) animals demonstrated highly significant (p < 0.001) neurological motor deficits that were sustained over the 1-week assessment period. Animals treated with MgSO ₄ at 30 minutes or at 8 or 12 hours postinjury demonstrated significantly improved motor outcomes compared with untreated control animals at all time points (0.001 < p < 0.05). Animals treated with MgSO ₄ at 24 hours had motor scores that were similar to those of untreated control animals early in the week, but demonstrated a significantly more rapid recovery in function and, by the end of the assessment period, they demonstrated significantly improved motor scores (p < 0.01). Repeated administration of MgSO ₄ over the 1-week observation period did not further improve outcome.

Conclusions. The present results demonstrate that Mg ⁺⁺ plays a neuroprotective role following severe diffuse traumatic axonal brain injury. Moreover, Mg ⁺⁺ therapy significantly improved motor outcome when administered up to 24 hours after injury, with early treatments providing the most significant benefit. Repeated administration beyond 24 hours postinjury did not provide additional neuroprotection.