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Browsing by Subject "brain-derived neurotrophic factor"
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Item Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration(Spandidos, 2016-10) Wang, Ying; Jia, Hua; Li, Wen-Yuan; Guan, Li-Xin; Deng, Lingxiao; Liu, Yan-Cui; Liu, Gui-Bo; Department of Anatomy and Cell Biology, IU School of MedicineThe present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.Item Post-Injury Treatment of 7,8-Dihydroxyflavone Promotes Neurogenesis in the Hippocampus of the Adult Mouse(Mary Ann Liebert, 2016-11-15) Zhao, Shu; Yu, Alex; Wang, Xiaoting; Gao, Xiang; Chen, Jinhui; Neurological Surgery, School of MedicineTraumatic brain injury (TBI) at the moderate level of impact induces massive cell death and results in extensive dendrite degeneration in the brain, leading to persistent cognitive, sensory, and motor dysfunction. Our previous reports have shown that adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus after receiving a moderate TBI with a controlled cortical impact (CCI) device. There is no effective approach to prevent immature neuron death or degeneration following TBI. Our recent study found that pretreatment of 7,8-dihydroxyflavone (DHF), a small molecule imitating brain-derived neurotrophic factor, protected immature neurons in the hippocampus from death following TBI. In the present study, we systemically treated moderate CCI-TBI mice or sham surgery mice with DHF once a day for 2 weeks via intraperitoneal injection, and then assessed the immature neurons in the hippocampus the 2nd day after the last DHF injection. We found that post-injury treatment of DHF for 2 weeks not only increased the number of adult-born immature neurons in the hippocampus, but also promoted their dendrite arborization in the injured brain following TBI. Thus, DHF may be a promising compound that can promote neurogenesis and enhance immature neuron development following TBI.