Repair of Spinal Cord Injury (SCI) Using Bone Marrow Stromal Cell Transfected with Adenoviral Vector Expressing Glial derived Neurotropic Factor (GDNF) in a Rat SCI Model

Back ground  Subsequent to spinal cord injury many pathological changes may occur that could lead to inappropriate environment for repair. The Most important of such changes is the death of neurons. Exogenous administration of growth factors that modulate neuronal survival, synaptic plasticity, and neurotransmission has been proposed as a potential therapeutic treatment for SCI. Among these growth factors, GDNF is a peptide with pleiotropic survival and growth-promoting effects on neurons. In addition, GDNF induces the growth of motor and sensory axons and inhibits neuronal apoptosis. Adult stem cells may provide new strategies to treat SCI. Among various types of candidate stem cells, bone marrow stromal cells (BMSC) are promising because they have shown potential to neuronal differentiation and repair in damaged spinal cord. In this study, we aimed to improve results of treatment using combination of BMSC and GDNF features. Methods: Rats were divided randomly into four groups of six. Spinal cord injury was then performed under general anesthesia using the weight dropping method. The BMSCs were injected on 3th day of post-spinal cord injury. Group one included rats receiving normal saline, group two received BMSC, group three received BMSC infected with adenoviruses encoding the beta-galactosidase gene, and group four received BMSC infected with adenoviruses encoding the GDNF gene. A Basso, Beattie and Bresnahan (BBB) score test was performed for a period of four weeks. Two weeks before the end of BBB, biotin dextran amine was injected intracerebrally followed by tissue staining at the end of the fourth week. Results: There was a significant difference in BBB scores between groups one and four (

Diabetes induces early transient changes in the content of vesicular transporters and no major effects in neurotransmitter release in hippocampus and retina

Diabetes induces changes in neurotransmitter release in central nervous system, which depend on the type of neurotransmitter and region studied. In this study, we evaluated the effect of diabetes (two and eight weeks duration) on basal and evoked release of [14C]glutamate and [3H]GABA in hippocampal and retinal synaptosomes. We also analyzed the effect of diabetes on the protein content of vesicular glutamate and GABA transporters, VGluT-1, VGluT-2 and VGAT, and on the α1A subunit of P/Q type calcium channels, which are abundant in nerve terminals. The protein content of vesicular glutamate and GABA transporters, and of the α1A subunit, was differently affected by diabetes in hippocampal and retinal synaptosomes. The changes were more pronounced in the retina than in hippocampus. VGluT-1 and VGluT-2 content was not affected in hippocampus. Moreover, changes occurred early, at two weeks of diabetes, but after eight weeks almost no changes were detected, with the exception of VGAT in the retina. Regarding neurotransmitter release, no major changes were detected. After two weeks of diabetes, neurotransmitter release was similar to controls. After eight weeks of diabetes, the basal release of glutamate slightly increased in hippocampus and the evoked GABA release decreased in retina. In conclusion, diabetes induces early transient changes in the content of glutamate and/or GABA vesicular transporters, and on calcium channels subunit, in retinal or hippocampal synaptosomes, but only minor changes in the release of glutamate or GABA. These results point to the importance of diabetes-induced changes in neural tissues at the presynaptic level, which may underlie alterations in synaptic transmission, particularly if they become permanent during the later stages of the disease