High-dose glucocorticoid treatment improves neurological recovery in head-injured mice

The ability of a single large intravenous dose of the sodium succinate esters of the glucocorticoids methylprednisolone, prednisolone, or hydrocortisone to enhance early neurological recovery after moderate to severe blunt head injury was examined in male CF-1 mice. Unanesthetized mice were restrained and subjected to a 900 gm-cm head injury produced by a 50-gm weight dropped 18 cm. This injury resulted in immediate loss of consciousness (loss of the righting reflex) in all animals, and death in approximately 30%. Survivors received a 0.1-ml tail vein injection of either vehicle or 15, 30, 60, or 120 mg/kg of methylprednisolone, prednisolone, or hydrocortisone within 5 minutes. Their neurological status was evaluated at 1 hour after injury. A 30-mg/kg dose of methylprednisolone was found to improve recovery significantly in comparison to that seen in vehicle-treated mice. A 15-mg/kg dose was less effective, and a 60- or 120-mg/kg dose was essentially ineffective. Prednisolone was also observed to improve neurological scores at 1 hour postinjury. A 60-mg/kg dose of prednisolone was optimal, while lower and higher doses had no effect. Hydrocortisone was unable to improve recovery over the wide dose range tested. The implications of these findings for the clinical management of head injury with glucocorticoid steroids are discussed.