The effects of methylprednisolone on prevention of brain edema after experimental moderate diffuse brain injury in rats--comparison between dosage, injection time, and treatment methods.
Our study was designed to determine whether methylprednisolone exerts a beneficial effect after experimental moderate diffuse brain injury and whether this possible beneficial effect is affected by the dosage, the timing of administration, and the methods of treatment. A total of 200 anesthetized adult rats were injured utilizing a weight-drop device through a Plexiglas guide tube. These rats were divided into eight groups: Group 1 (n = 35) was assigned to receive no methylprednisolone after impact (control group), Group 2 (n = 25) received an initial intraperitoneal administration of methylprednisolone with a dose of 5 mg/kg at 1 hour after cranial impact, followed by administration with a maintenance dose of 5 mg/kg/4 hours. Group 3 (n = 25), group 5 (n = 25), and group 7 (n = 20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours, respectively without a maintenance dose. Group 4 (n = 25), group 6 (n = 25), and group 8 (n = 20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours after impact, with a maintenance dose of 15 mg/kg/4 hours. Measured water content of brain tissue expressed the amount of water as the difference between fresh and dry weight. At 48 hours after impact, the water content in group 4 and 6 were significantly lower than group 1. Mean +/- SD was 61.4 +/- 0.37% in group 4 (p < 0.03), 61.5 +/- 0.34% in group 6 (p < 0.001), and 63.6 +/- 0.48% in group 1. Compared to group 1, the difference was not statistically significant in group 2 (p > 0.1), group 3 (p > 0.5), group 5 (p > 0.6), group 7 (p > 0.1), and group 8 (p > 0.5). Groups treated with mega dose before 4 hours after head injury, including maintenance dose, showed beneficial effects. Our study suggests that the efficacy of methylprednisolone in head injury was related to the dosage, the timing of administration, and method of treatment.
Park
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Department of Neurosurgery, Inha Hospital, College of Medicine, Inha University, Sung Nam City, Korea.
D000818:Animals; D001929:Brain Edema / Q000517:prevention & control*; D001930:Brain Injuries / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008775:Methylprednisolone / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D008775:Methylprednisolone