title: Early transplantation of bone marrow mononuclear cells promotes neuroprotection and modulation of inflammation after status epilepticus in mice by paracrine mechanisms.
abstract: 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.
authors.affiliation: Hospital São Rafael, Av. São Rafael, 2152. São Marcos, Salvador, BA, 41253-190, Brazil.
authors.forename: Marcos Maurício Tosta
authors.initials: MM
authors.lastname: Leal
authors.forename: Zaquer Suzana Munhoz
authors.initials: ZS
authors.lastname: Costa-Ferro
authors.forename: Bruno Solano de Freitas
authors.initials: BS
authors.lastname: Souza
authors.forename: Carine Machado
authors.initials: CM
authors.lastname: Azevedo
authors.forename: Thiago Meneses
authors.initials: TM
authors.lastname: Carvalho
authors.forename: Carla Martins
authors.initials: CM
authors.lastname: Kaneto
authors.forename: Rejane Hughes
authors.initials: RH
authors.lastname: Carvalho
authors.forename: Ricardo Ribeiro
authors.initials: RR
authors.lastname: Dos Santos
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D018696:Neuroprotective Agents; D010862:Pilocarpine / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013226:Status Epilepticus / Q000139:chemically induced* / Q000601:surgery
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018696:Neuroprotective Agents; D010862:Pilocarpine; D049452:Green Fluorescent Proteins