RESUMO
BACKGROUND AND PURPOSE: Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies. METHODS: In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation. RESULTS: Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants. CONCLUSIONS: These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.
Assuntos
Transplante de Tecido Encefálico , Plexo Corióideo , Infarto da Artéria Cerebral Média/cirurgia , Transplante Heterólogo , Transplante Heterotópico , Alginatos , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Morte Celular , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Córtex Cerebral/citologia , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Plexo Corióideo/metabolismo , Meios de Cultivo Condicionados/farmacologia , Composição de Medicamentos , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Gliose/etiologia , Ácido Glucurônico , Ácidos Hexurônicos , Infarto da Artéria Cerebral Média/patologia , Masculino , Atividade Motora , Fator de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Sus scrofaRESUMO
Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA. Histological analysis demonstrated that choroid plexus transplants reduced the volume of striatal damage and protected ChAT-, but not NADPH-diaphorase-positive neurons. These data are the first to demonstrate that transplanted choroid plexus cells can protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.