Effects of Brain‐Derived Neurotrophic Factor (BDNF) on Compression‐Induced Spinal Cord Injury: BDNF Attenuates Down‐Regulation of Superoxide Dismutase Expression and Promotes Up‐Regulation of Myelin Basic Protein Expression

Osamu Ikeda, M. Murakami, H. Ino, M. Yamazaki, M. Koda, H. Moriya
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引用次数: 91

Abstract

Neurotrophins enhance the survival of cells in the nervous system under both physiological and pathological conditions, such as those caused by disease or trauma. We recently demonstrated that expression of brain-derived neurotrophic factor (BDNF) was up-regulated in neurons and glia after compression-induced spinal cord injury (SCI). We show here the effects of BDNF on the oligodendrocyte survival and functional recovery after SCI. The effects of intrathecally administered BDNF on both Cu/Zn superoxide dismutase (CuZnSOD) and myelin basic protein (MBP) expression were examined using rats that had received compression-induced spinal cord injury. CuZnSOD expression in the spinal cord was down-regulated within 24 h of compression-induced injury and then recovered. Continuous infusion of BDNF inhibited the acute down-regulation of CuZnSOD expression. In situ hybridization showed that CuZnSOD was expressed in both neurons and glia. Although MBP expression was greatly reduced after injury, BDNF administration promoted the recovery of MBP expression nearly to a control level after 2 wk. Furthermore, BDNF administration also prompted behavioral recovery. These results suggest BDNF's usefulness in human clinical applications. The attenuation of CuZnSOD down-regulation may be related to a protective effect of BDNF and the promotion of MBP up-regulation may be related to a long-lasting restorative effect.
脑源性神经营养因子(BDNF)对压迫性脊髓损伤的影响:BDNF减弱超氧化物歧化酶表达的下调,促进髓鞘碱性蛋白表达的上调
神经营养因子在生理和病理条件下,如疾病或创伤引起的情况下,增强神经系统细胞的存活率。我们最近证实,脊髓损伤(SCI)后,脑源性神经营养因子(BDNF)在神经元和胶质细胞中的表达上调。我们在这里展示了BDNF对脊髓损伤后少突胶质细胞存活和功能恢复的影响。采用脊髓受压损伤大鼠,观察鞘内给予BDNF对Cu/Zn超氧化物歧化酶(CuZnSOD)和髓鞘碱性蛋白(MBP)表达的影响。脊髓CuZnSOD表达在挤压损伤24 h内下调后恢复。持续输注BDNF可抑制CuZnSOD表达的急性下调。原位杂交表明,CuZnSOD在神经元和胶质细胞中均有表达。虽然损伤后MBP表达显著降低,但BDNF使MBP表达在2周后恢复到接近控制水平。此外,给予BDNF也促进行为恢复。这些结果表明BDNF在人类临床应用中的有效性。CuZnSOD下调的减弱可能与BDNF的保护作用有关,而MBP上调的促进可能与持久的恢复作用有关。
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