Terayama R, Bando Y, Murakami K, Kato K, Kishibe M, Yoshida S
Department of Functional Anatomy and Neuroscience, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan.
Neuroscience. 2007 Aug 10;148(1):175-87. doi: 10.1016/j.neuroscience.2007.05.037. Epub 2007 Jul 12.
Previous studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the CNS. The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin(-/-)) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin(-/-) mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI. Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin(-/-) mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin(-/-) mice compared with WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.
先前的研究表明，丝氨酸蛋白酶神经纤溶酶在中枢神经系统损伤后成熟少突胶质细胞中表达上调。脊髓损伤（SCI）的病理生理学涉及原发性和继发性机制，后者进一步导致功能的永久性丧失。为了探究神经纤溶酶在脊髓损伤后的作用，我们使用挤压损伤模型（一种特征明确且可重复的脊髓损伤模型）对野生型（WT）和神经纤溶酶缺陷型（neuropsin(-/-)）小鼠进行了组织化学和行为学分析。原位杂交显示，挤压脊髓损伤后野生型小鼠脊髓白质中神经纤溶酶mRNA表达上调，在第4天达到峰值。脊髓损伤后，神经纤溶酶缺陷型小鼠的脱髓鞘、少突胶质细胞死亡和轴突损伤均有所减轻。虽然脊髓损伤后两种品系小鼠损伤部位尾侧皮质脊髓束的轴突变性均很明显，但神经纤溶酶缺陷型小鼠损伤部位尾侧存活神经纤维的数量明显多于野生型小鼠。行为学分析显示，尽管两种品系小鼠均因脊髓损伤而出现严重的初始后肢功能障碍，但与野生型小鼠相比，神经纤溶酶缺陷型小鼠在第10 - 42天的恢复情况明显更好。这些观察结果表明，神经纤溶酶参与了由脱髓鞘、少突胶质细胞死亡和轴突变性介导的脊髓损伤发病机制的继发性阶段。
