Trauma-induced glial proliferation: possible involvement of the immune system

Rat neurologlial cells proliferate following trauma to the frontal cortex. Since previous reports have indicated that activated T-lymphocytes secrete a factor which can induce the proliferation of glial cells in vitro, we investigated the effects of immunosuppression on the trauma-induced proliferation of glial cells in the rat. Animals were treated with either methotrexate (2.5 and 10 mg/kg/day), hydrocortisone (100 mg/kg/day), or saline for five days prior to lesioning of the cortex. Immunocompetence was estimated by measuring sheep red blood cell hemagglutination titers at the time of killing. On the last day of drug treatment, rats were mechanically lesioned on the frontal cortex, and the incorporation of intraventricularly injected 3H-thymidine (3H-TdR) into cortical DNA, a measure of glial cell proliferation, was determined two days after lesioning. Intraperitoneal treatment with methotrexate before the lesioning depressed 3H-TdR incorporation into brain DNA, and reduced hemagglutination titers and thymus and spleen weight. However, intramuscular hydrocortisone pretreatment, which had immunosuppressive actions similar to methotrexate, had a much smaller effect on 3H-TdR incorporation into brain DNA following trauma. Methotrexate given acutely after lesioning did not depress thymidine utilization in the lesioned rat cortex, apparently because of poor penetration of the folate analog into the brain. Thus, we conclude that inhibition of glial cell proliferation resulting from methotrexate pretreatment had been produced indirectly, probably by its severe immunosuppressive effects.