RESUMO
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-1ß, 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.
Assuntos
Transplante de Medula Óssea , Fármacos Neuroprotetores , Pilocarpina/administração & dosagem , Estado Epiléptico/induzido quimicamente , Animais , Sequência de Bases , Citocinas/biossíntese , Primers do DNA , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estado Epiléptico/cirurgiaRESUMO
The distribution of bone marrow cells in brain areas during the acute period after pilocarpine-induced status epiepticus (SE) was investigated here. To achieve this, we generated chimeric mice by engrafting bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic mice. GFP(+) bone marrow-derived cells were found throughout the brain, predominantly in the hippocampus. As expected, these cells exhibited the characteristics of microglia. The pattern of distribution, proliferation, and differentiation of GFP(+)cells changes as a function of intensity and time following SE. This pattern is also a consequence of the inflammatory response, which is followed by the progressive neuronal damage that is characteristic of the pilocarpine model.
Assuntos
Células da Medula Óssea/fisiologia , Transplante de Medula Óssea/métodos , Encéfalo/cirurgia , Proliferação de Células , Estado Epiléptico/cirurgia , Animais , Encéfalo/patologia , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Pilocarpina/efeitos adversos , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/patologia , Fatores de TempoRESUMO
In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.
Assuntos
Transplante de Medula Óssea/métodos , Convulsões/prevenção & controle , Estado Epiléptico/cirurgia , Análise de Variância , Animais , Antígenos CD/metabolismo , Movimento Celular/fisiologia , Modelos Animais de Doenças , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/fisiologia , Citometria de Fluxo , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/genética , Hipocampo/patologia , Técnicas In Vitro , Lítio , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Pilocarpina , Ratos , Ratos Wistar , Convulsões/etiologia , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/complicações , Estado Epiléptico/patologia , Fatores de TempoRESUMO
Status epilepticus (SE) represents a medical emergency that annually affects 60,000--150,000 individuals in the United States. Selective neuronal loss in vulnerable areas has been pathologically demonstrated following convulsive SE primarily affecting the limbic system, thalamus and cerebellum. Morbidity in those cases that follow refractory SE (RSE) is poorly documented. There have been anecdotal reports of surgical treatment for this condition, especially secondary to brain lesions. We report a 6-year-old patient who was in RSE for 60 days, without a brain lesion documented by MRI. The patient underwent multiple subpial transection (MST) of the sensorimotor cortex, which by ictal EEG and ictal SPECT proved to be the epileptogenic zone. We conclude that MST should be considered as an alternative treatment for refractory partial SE.
Assuntos
Córtex Motor/cirurgia , Estado Epiléptico/cirurgia , Criança , Eletrocardiografia/métodos , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Monitorização Intraoperatória/métodos , Córtex Motor/patologia , Pia-Máter/cirurgia , Estado Epiléptico/diagnóstico , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Five years old, female, who started with tonic-clonic seizures on the right side of the body, with vomits and unconsciousness. The patient had been hospitalized for eight times in the last sixty days because of seizures. At physical exam, she had a severe arterial hypertension (270/140 mmHg). The computerized tomographic scan and magnetic resonance imaging revealed hypodense areas, mainly on the right parietal-temporal region, suggesting presence of edema. The angiography showed stenosis of the right renal artery, that was the cause of arterial hypertension. After the control of arterial hypertension by nephrectomy, the patient had a complete remission of the symptoms, as well as the images anomalies.