RESUMO
This study evaluated the effect of microglia transplantation on neurological functional recovery in rats subjected to traumatic spinal cord injury (SCI). The rat model of SCI was established using a weight drop device. Forty SCI rats were randomly divided into the microglia group and the saline group. Then, rat-derived microglial cells or normal saline was injected into the injured site 7 days after surgery. The Basso-Beattie-Bresnahan (BBB) score, inclined plate test, and motor-evoked potentials (MEPs) were applied to assess the recovery of motor function. Hematoxylin and eosin (H&E) staining was used to assess the therapeutic effect. Microglia transplantation significantly improved BBB scores and functional scores at 2, 3, 4, 6, and 8 weeks after surgery compared to saline injection (P<0.05). Meanwhile, a prolonged MEP latency and decreased MEP amplitude were observed at 4 and 8 weeks in the microglia group (P<0.05). Histological analysis showed less damage and better prognosis in SCI rats of the microglia group. BrdU+ cell tracing experiments showed that microglia were recruited to the injured area of the spinal cord at 7 and 14 days after transplantation. The intensity of immunofluorescence was increased in CD68+ and OX42+ microglia at 2 days, 1 week, and 2 weeks, and then decreased at 3 and 4 weeks after transplantation in the microglia group. The transplantation of activated microglia played a key role in promoting the recovery of spinal cord function in a rat model of SCI.
Assuntos
Animais , Feminino , Ratos , Traumatismos da Medula Espinal/cirurgia , Microglia/transplante , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologia , Fatores de Tempo , Distribuição Aleatória , Ratos Wistar , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
l-3, 4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson's disease but can induce debilitating abnormal involuntary movements (dyskinesia). Here we show that the development of L-DOPA-induced dyskinesia in the rat is accompanied by upregulation of an inflammatory cascade involving nitric oxide. Male Wistar rats sustained unilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. After three weeks animals started to receive daily treatment with L-DOPA (30 mg/kg plus benserazide 7.5 mg/kg, for 21 days), combined with an inhibitor of neuronal NOS (7-nitroindazole, 7-NI, 30 mg/kg/day) or vehicle (saline-PEG 50%). All animals treated with L-DOPA and vehicle developed abnormal involuntary movements, and this effect was prevented by 7-NI. L-DOPA-treated dyskinetic animals exhibited an increased striatal and pallidal expression of glial fibrillary acidic protein (GFAP) in reactive astrocytes, an increased number of CD11b-positive microglial cells with activated morphology, and the rise of cells positive for inducible nitric oxide-synthase immunoreactivity (iNOS). All these indexes of glial activation were prevented by 7-NI co-administration. These findings provide evidence that the development of L-DOPA-induced dyskinesia in the rat is associated with activation of glial cells that promote inflammatory responses. The dramatic effect of 7-NI in preventing this glial response points to an involvement of nitric oxide. Moreover, the results suggest that the NOS inhibitor prevents dyskinesia at least in part via inhibition of glial cell activation and iNOS expression. Our observations indicate nitric oxide synthase inhibitors as a therapeutic strategy for preventing neuroinflammatory and glial components of dyskinesia pathogenesis in Parkinson's disease.