title: Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats.
abstract: 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.
authors.affiliation: Instituto de Pesquisas Biomédicas e Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Zaquer S M
authors.initials: ZS
authors.lastname: Costa-Ferro
authors.forename: Bruno S F
authors.initials: BS
authors.lastname: Souza
authors.forename: Marcos M T
authors.initials: MM
authors.lastname: Leal
authors.forename: Carla Martins
authors.initials: CM
authors.lastname: Kaneto
authors.forename: Carine Machado
authors.initials: CM
authors.lastname: Azevedo
authors.forename: Igor Campos
authors.initials: IC
authors.lastname: da Silva
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro-dos-Santos
authors.forename: Jaderson C
authors.initials: JC
authors.lastname: Dacosta
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D015994:Incidence; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000637:transplantation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators