Recovery of brain dysfunction after methylmercury exposure in rats

We studied the time course of central nervous system (CNS) involvement afte r the termination of methylmercury exposure to rats, in order to investigat e whether or not the involvement still progresses even after the terminatio n of exposure. Methylmercury chloride (MMC), at a dose of 2 mg/kg/day, was subcutaneously injected for 25 consecutive days in 12 adult male Sprague-Da wley rats. Six of them were sacrificed on the final day of exposure (group A) after completing the observations of behavioral changes and determining the local cerebral glucose utilization (LCGU) as an indicator of cerebral n euronal activities. Histological examinations of the brain and the sciatic nerve were done. The other six rats were further followed up for 90 days af ter the termination of exposure (group B). In addition, six rats that recei ved physiological saline served as a control. Group A showed a significant reduction of LCGU without any accompanying cerebral histological alteration s and a moderate loss of myelinated fibers in the sciatic nerve. Group B sh owed normal LCGU rates while severe axonal degeneration of the sciatic nerv e was found on the final day of the 90-day follow-up period. The present re sults demonstrate that a transient involvement of the CNS can occur after M MC exposure. In addition, a complete recovery may occur when the process is mild enough not to cause histological alterations. In contrast, the involv ement of the peripheral nerve is much more severe than that of the CNS and it was observed to progress even after the cessation of MMC exposure. There fore, it seems unlikely, at least in rats, that a steadily progressive cour se occurs in the CNS but not in the peripheral nerves over a long period of time after MMC exposure. (C) 2000 Elsevier Science B.V. All rights reserve d.