Approximately 30% of patients with mesial temporal lobe epilepsy do not respond to treatment with antiepileptic drugs. We have previously shown that transplantation of mononuclear bone marrow cells (BMC) has an anticonvulsant effect in acute epilepsy. Here, we used pilocarpine to induce epilepsy in rats and studied the effects of BMC injected intravenously either at the onset of seizures or after 10 months of recurrent seizures. BMC effectively decreased seizure frequency and duration. In addition, decreased levels of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and increased levels of anti-inflammatory cytokine (IL-10) were observed in the brain and serum of BMC-treated rats. Transplants performed at seizure-onset protected against pilocarpine-induced neuronal loss and gliosis and stimulated the proliferation of new neurons in epileptic rats. Our data demonstrate that BMC transplantation has potent therapeutic effects and could be a potential therapy for clinically intractable epilepsies.

Status epilepticus (SE) is a severe clinical manifestation of epilepsy associated with intense neuronal loss and inflammation, two key factors involved in the pathophysiology of temporal lobe epilepsy. Bone marrow mononuclear cells (BMMC) attenuated the consequences of pilocarpine-induced SE, including neuronal loss, in addition to frequency and duration of seizures. Here we investigated the effects of BMMC transplanted early after the onset of SE in mice, as well as the involvement of soluble factors produced by BMMC in the effects of the cell therapy. Mice were injected with pilocarpine for SE induction and randomized into three groups: transplanted intravenously with 1 × 10(7) BMMC isolated from GFP transgenic mice, injected with BMMC lysate, and saline-treated controls. Cell tracking, neuronal counting in hippocampal subfields and cytokine analysis in the serum and brain were performed. BMMC were found in the brain 4 h following transplantation and their numbers progressively decreased until 24 h following transplantation. A reduction in hippocampal neuronal loss after SE was found in mice treated with live BMMC and BMMC lysate when compared to saline-treated, SE-induced mice. Moreover, the expression of inflammatory cytokines IL-1β, TNF-α, IL-6 was decreased after injection of live BMMC and to a lesser extent, of BMMC lysate, when compared to SE-induced controls. In contrast, IL-10 expression was increased. Analysis of markers for microglia activation demonstrated a reduction of the expression of genes related to type 1-activation. BMMC transplantation promotes neuroprotection and mediates anti-inflammatory effects following SE in mice, possibly through the secretion of soluble factors.

Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.

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RESUMONo Brasil é corriqueiro o uso da flora nativa sem respaldo científico de suas propriedades, indicação e dose terapêutica, forma de preparo, outrossim interações medicamentosas. Somado a isso, a notificação dos casos de intoxicação por plantas não é obrigatória, favorecendo a elevação dos casos. Sendo assim, o objetivo deste manuscrito foi discorrer sobre a situação atual do Brasil frente a quadros de intoxicação por plantas comumente utilizadas e suas características, mediante revisão de dados em bases científicas. Foi realizada uma revisão sistemática com dados do Sistema Nacional de Informações Tóxico-Farmacológicas (SINITOX) e de bases de dados como a Scientific Electronic Library Online, nos idiomas português e inglês. Verificou-se que a ingestão de plantas, incluindo as medicinais em níveis tóxicos, pode causar alterações nos sistemas circulatório, gastrointestinal e nervoso central, podendo ser fatal. Os compostos bioativos mais encontrados em plantas tóxicas são os alcaloides, glicosídeos cardiotônicos e cianogênios, taninos, saponinas, oxalato de cálcio e toxialbuminas. Os dados mais recentes do SINITOX datam de 2016 a 2017, no qual foram identificados 2.028 casos de intoxicações por plantas, 1,17% do total das intoxicações no mesmo período por todas as causas registradas, com 4 óbitos (0,20%), das quais o público infantil de 1 a 9 anos foi o mais afetado com 1.065 casos (52,51%), seguido por adultos 490 casos (24,16%), adolescentes com 121 casos (5,97%) e idosos com 119 casos (5,87%), em sua maioria no meio urbano 1.459 registros (71,94%). As causas mais frequentes são as acidentais, ignorância e o suicídio, predominantemente do sexo masculino, sendo as regiões Sul, sudeste e centro-oeste as mais afetadas, respectivamente. Logo, evidencia-se a necessidade de uma participação mais expressiva dos Centros de Informação e Assistência Toxicológica para evitar a subnotificação dos índices, visto que a maioria das causas descritas seriam evitadas mediante uma política de educação em saúde sobre os grupos de risco, otimizando ainda os recursos públicos ao reduzir a ocupação de leitos hospitalares, medicamentos, antídotos e demais tecnologias.