RESUMEN
We recently demonstrated that blood-brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood-brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic-ischaemic (HI) injury model. Seven-day-old Sprague-Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post-transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme-linked immunosorbent assay at day 3 post-transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up-regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor-mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood-brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.
Asunto(s)
Conducta Animal/efectos de los fármacos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Hipoxia-Isquemia Encefálica/patología , Hipoxia-Isquemia Encefálica/terapia , Manitol/farmacología , Factores de Crecimiento Nervioso/genética , Regulación hacia Arriba/efectos de los fármacos , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Supervivencia Celular/efectos de los fármacos , Dendritas/efectos de los fármacos , Dendritas/patología , Supervivencia de Injerto/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Hipoxia-Isquemia Encefálica/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Five cases of patients with the Rett syndrome are reported. The criteria for this diagnosis in these cases are discussed. These are the first cases of the Rett syndrome reported in Brazil and the authors call attention to the fact that this syndrome seems to be in our country as frequent as in USA, Europe and Japan where it has been more studied.
Asunto(s)
Ataxia/diagnóstico , Trastorno Autístico/diagnóstico , Demencia/diagnóstico , Brasil , Cefalometría , Niño , Preescolar , Femenino , Humanos , Desempeño Psicomotor , Conducta Estereotipada , SíndromeRESUMEN
Cinco casos de pacientes com a síndrome de Rett säo estudados. Os critérios diagnósticos säo discutidos. Estes säo os primeiros casos de síndrome de Rett relatados no Brasil. Chama-se atençäo para o fato de esta entidade parecer ser em nosso país täo freqüente quanto nos EUA, Europa e Japäo onde ela tem sido bastante estudada