Gianina Teribele Venturin

Bone marrow mononuclear cells reduce seizure frequency and improve cognitive outcome in chronic epileptic rats.

AIMSnEpilepsy affects 0.5-1% of the worlds population, and approximately a third of these patients are refractory to current medication. Given their ability to proliferate, differentiate and regenerate tissues, stem cells could restore neural circuits lost during the course of the disease and reestablish the physiological excitability of neurons. This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) on seizure control and cognitive impairment caused by experimentally induced epilepsy.nnnMAIN METHODSnStatus epilepticus (SE) was induced by lithium-pilocarpine injection and controlled with diazepam 90 min after SE onset. Lithium-pilocarpine-treated rats were intravenously transplanted 22 days after SE with BMMCs obtained from enhanced green fluorescent protein (eGFP) transgenic C57BL/6 mice. Control epileptic animals were given an equivalent volume of saline or fibroblast injections. Animals were video-monitored for the presence of spontaneous recurrent seizures prior to and following the cell administration procedure. In addition, rats underwent cognitive evaluation using a Morris water maze.nnnKEY FINDINGSnOur data show that BMMCs reduced the frequency of seizures and improved the learning and long-term spatial memory impairments of epileptic rats. EGFP-positive cells were detected in the brains of transplanted animals by PCR analysis.nnnSIGNIFICANCEnThe positive behavioral effects observed in our study indicate that BMMCs could represent a promising therapeutic option in the management of chronic temporal lobe epilepsy.

Potencial terapêutico das células-tronco de medula óssea no tratamento da epilepsia

Epilepsia e uma patologia bastante prevalente no nosso meio. Ha um numero significativo de pacientes que nao obtem resposta com a terapeutica medicamentosa, o que motivou a pesquisa de novas terapeuticas. O conceito de neurogenese no cerebro adulto, hoje ja amplamente conhecida, principalmente a que ocorre na zona subventricular e na zona subgranular do giro denteado, motivou o desenvolvimeto de tecnicas que aproveitassem esse mecanismo na tentativa de obtencao de efeitos antiepileptogenicos e reparadores. A maior parte dos estudos em vigencia hoje, e que buscam tal finalidade, trabalha o uso de transplante de celulas progenitoras neurais ou de celulas fetais em modelos experimentais. No entanto, a terapeutica com celulas-tronco de medula ossea parece bastante interessante e promissora. Em doencas neurologicas nas quais os danos sao frequentemente irreversiveis, as estrategias regenerativas podem representar um novo caminho. Em nosso laboratorio, temos estudado o potencial terapeutico de celulas-tronco da medula ossea no controle de crises espontâneas recorrentes associadas ao modelo da pilocarpina com resultados excelentes. Tambem ja esta em andamento o primeiro estudo em humanos utilizando celulas-tronco de medula ossea para o tratatamento da epilepsia.