Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice

Associacao Beneficente de Coleta de Sangue da Fundacao de Apoio a Pesquisa- UNIFESP (FAP-Colsan) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-alpha after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells.Results: Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels.Conclusions: Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies. Universidade Federal de São Paulo, UNIFESP, Dept Fisiol, Lab Neurofisiol, BR-04023066 São Paulo, Brazil Universidade Federal de São Paulo, Disciplina Imunol, Dept Microimunoparasitol, São Paulo, Brazil Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil Hosp Sao Rafael, Ctr Biotecnol & Terapia Celular, Salvador, BA, Brazil Universidade Federal de São Paulo, UNIFESP, Dept Fisiol, Lab Neurofisiol, BR-04023066 São Paulo, Brazil Universidade Federal de São Paulo, Disciplina Imunol, Dept Microimunoparasitol, São Paulo, Brazil Web of Science