Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats

被引:44
作者
Costa-Ferro, Zaquer S. M. [1 ,2 ,3 ]
Souza, Bruno S. F. [3 ,4 ]
Leal, Marcos M. T. [3 ]
Kaneto, Carla Martins [3 ]
Azevedo, Carine Machado [3 ]
da Silva, Igor Campos [3 ,5 ]
Soares, Milena B. P. [3 ,4 ]
Ribeiro-dos-Santos, Ricardo [3 ]
DaCosta, Jaderson C. [1 ,2 ]
机构
[1] Pontificia Univ Catolica Rio Grande Sul PUCRS, Inst Cerebro, BR-90610000 Porto Alegre, RS, Brazil
[2] Pontificia Univ Catolica Rio Grande Sul PUCRS, Inst Pesquisas Biomed, BR-90610000 Porto Alegre, RS, Brazil
[3] Hosp Sao Rafael, Ctr Biotecnol & Terapia Celular, Salvador, BA, Brazil
[4] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil
[5] Hosp Sao Rafael, Serv Anat Patol & Citopatol, Salvador, BA, Brazil
关键词
Temporal lobe epilepsy; Bone marrow mononuclear cells; Seizure frequency; Neuronal loss; Cytokines; Pilocarpine; TEMPORAL-LOBE EPILEPSY; HEMATOPOIETIC CYTOKINES; CEREBRAL INFARCTION; THERAPEUTIC WINDOW; SUBACUTE PHASE; BRAIN-INJURY; EXPRESSION; PILOCARPINE; ASTROCYTES; GLUTAMATE;
D O I
10.1016/j.nbd.2011.12.001
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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-alpha, IL-1 beta 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. (C) 2012 Elsevier Inc. All rights reserved.a
引用
收藏
页码:302 / 313
页数:12
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