Epileptogenic activity of granulomas associated with murine cysticercosis

Abstract

Neurocysticercosis, caused by Taenia solium, is a common cause of neurologic disease in developing countries and among immigrants to the United States. Seizures are the most common clinical manifestation of neurocysticercosis. Imaging studies of patients with seizures from neurocysticercosis typically reveal evidence of an inflammatory reaction associated with the parasite or calcified granulomas. This study investigated whether a substance produced by the host granulomatous reaction to the dying parasite, in a mouse model of the infection, is sufficient to induce epileptiform activity. Granulomas associated with Taenia crassiceps cysticerci were removed from the peritoneal cavity of infected mice. One piece of the granuloma was used for blinded histological staging of the dying parasite. The second piece was used to generate extracts, which were injected into the hippocampus of an anesthetized Sprague-Dawley rat. Positive controls included animals injected with kainic acid, picrotoxin, or bicuculline. Seizures were recorded after injection of extracts from 6 out of 6 early stage granulomas, but only 1 out of 9 late stage granulomas. Injections of buffered saline, extracts from non-stimulated mouse spleen cells, and homogenates of viable parasite material caused no epileptiform activity. The data suggest that a substance in the granulomas early in the inflammatory response to the dying parasite is capable of inducing seizure activity. Further experiments are needed to dissect out the exact seizure mediator in the granuloma extracts.