Spinal Glia Division Contributes to Conditioning Lesion-Induced Axon Regeneration Into the Injured Spinal Cord: Potential Role of Cyclic AMP-Induced Tissue Inhibitor of Metalloproteinase-1.
Spinal Glia Division Contributes to Conditioning Lesion-Induced Axon Regeneration Into the Injured Spinal Cord: Potential Role of Cyclic AMP-Induced Tissue Inhibitor of Metalloproteinase-1.
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DOI：
10.1097/nen.0000000000000192
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发表时间：
2015-06
影响因子：
3.2
通讯作者：
Shubayev VI
中科院分区：
文献类型：
--
作者：
Liu H;Angert M;Nishihara T;Shubayev I;Dolkas J;Shubayev VI
脊髓损伤后感觉神经元的再生依赖于神经胶质抗原2（NG 2）表达细胞的分裂功能。我们已经证明，通过短期药理学抑制基质金属蛋白酶，NG 2阳性细胞分裂数量的增加有助于脊髓损伤后的恢复。脊髓损伤前的条件性坐骨神经挤压（SNC）通过环磷酸腺苷的神经节内作用刺激中枢感觉轴突再生。在这里，使用溴脱氧尿苷，丝裂霉素（有丝分裂抑制剂），和霍乱毒素B示踪剂，我们证明，SNC诱导的脊髓胶质细胞的分裂与脊髓诱导的金属蛋白酶组织抑制剂-1，并有助于中央感觉轴突生长到受损的脊髓。分裂细胞主要是NG 2阳性和Iba 1阳性，包括髓样NG 2阳性群体。响应SNC而分裂的细胞主要成熟为损伤脊髓内的少突胶质细胞和小胶质细胞。一些有丝分裂后的细胞保持NG 2反应，并与再生纤维。此外，神经节内的金属蛋白酶-1的组织抑制剂的表达诱导后，SNC或环腺苷酸类似物（dbcAMP）的背根神经节在体内和在初级成人背根神经节文化。总的来说，这些研究结果支持一种新的模型，即环磷酸腺苷激活的再生程序诱导的感觉神经元的调节周围神经病变使用金属蛋白酶-1的组织抑制剂，以防止短期蛋白水解，使神经胶质细胞分裂，促进轴突生长到受损的中枢神经系统。
Regeneration of sensory neurons after spinal cord injury depends on the function of dividing neuronal-glial antigen 2 (NG2)–expressing cells. We have shown that increases in the number of dividing NG2-positive cells through short-term pharmacologic inhibition of matrix metalloproteinases contributes to recovery after spinal cord injury. A conditioning sciatic nerve crush (SNC) preceding spinal cord injury stimulates central sensory axon regeneration via the intraganglionic action of cyclic adenosine monophosphate. Here, using bromodeoxyuridine, mitomycin (mitosis inhibitor), and cholera toxin B tracer, we demonstrate that SNC-induced division of spinal glia is related to the spinal induction of tissue inhibitor of metalloproteinase-1 and contributes to central sensory axon growth into the damaged spinal cord. Dividing cells were mainly NG2-positive and Iba1-positive and included myeloid NG2-positive populations. The cells dividing in response to SNC mainly matured into oligodendrocytes and microglia within the injured spinal cord. Some postmitotic cells remained NG2-reactive and were associated with regenerating fibers. Moreover, intraganglionic tissue inhibitor of metalloproteinase-1 expression was induced after administration of SNC or cyclic adenosine monophosphate analog (dbcAMP) to dorsal root ganglia in vivo and in primary adult dorsal root ganglia cultures. Collectively, these findings support a novel model whereby a cyclic adenosine monophosphate–activated regeneration program induced in sensory neurons by a conditioning peripheral nerve lesion uses tissue inhibitor of metalloproteinase-1 to protect against short-term proteolysis, enabling glial cell division and promoting axon growth into the damaged CNS.