Physician Assistant Program, Department of Biology, Slippery Rock University, Slippery Rock Pennsylvania, Slippery Rock, PA, USA.
Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA.
J Neurosci Res. 2021 Apr;99(4):1009-1023. doi: 10.1002/jnr.24780. Epub 2021 Jan 16.
Axonal damage and the subsequent interruption of intact neuronal pathways in the spinal cord are largely responsible for the loss of motor function after injury. Further exacerbating this loss is the demyelination of neighboring uninjured axons. The post-injury environment is hostile to repair, with inflammation, a high expression of chondroitin sulfate proteoglycans (CSPGs) around the glial scar, and myelin breakdown. Numerous studies have demonstrated that treatment with the enzyme chondroitinase ABC (cABC) creates a permissive environment around a spinal lesion that permits axonal regeneration. Neurotrophic factors like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophic factor-3 (NT-3), and ciliary neurotrophic factor (CNTF) have been used to promote neuronal survival and stimulate axonal growth. CSPGs expressed near a lesion also inhibit migration and differentiation of endogenous oligodendrocyte progenitor cells (OPCs) in the spinal cord, and cABC treatment can neutralize this inhibition. This study examined the neurotrophins commonly used to stimulate axonal regeneration after injury and their potential effects on OPCs cultured in the presence of CSPGs. The results reveal differential effects on OPCs, with BDNF and GDNF promoting process outgrowth and NT-3 stimulating differentiation of OPCs, while CNTF appears to have no observable effect. This finding suggests that certain neurotrophic agents commonly utilized to stimulate axonal regeneration after a spinal injury may also have a beneficial effect on the endogenous oligodendroglial cells as well.
轴突损伤以及脊髓中完整神经元通路的后续中断在很大程度上导致了损伤后的运动功能丧失。邻近未受伤轴突脱髓鞘进一步加剧了这种丧失。损伤后的环境不利于修复，存在炎症、神经胶质瘢痕周围软骨素硫酸盐蛋白聚糖 (CSPG) 的高表达以及髓鞘破裂。许多研究表明，用酶软骨素酶 ABC (cABC) 治疗会在脊髓损伤部位周围产生一个允许轴突再生的许可环境。神经营养因子，如脑源性神经营养因子 (BDNF)、胶质细胞源性神经营养因子 (GDNF)、神经营养因子-3 (NT-3) 和睫状神经营养因子 (CNTF)，已被用于促进神经元存活和刺激轴突生长。在损伤部位附近表达的 CSPG 也抑制脊髓内内源性少突胶质前体细胞 (OPC) 的迁移和分化，而 cABC 治疗可以中和这种抑制作用。本研究检查了常用于损伤后刺激轴突再生的神经营养因子及其在 CSPG 存在下对 OPC 的潜在影响。结果显示对 OPC 具有不同的影响，BDNF 和 GDNF 促进突起生长，NT-3 刺激 OPC 分化，而 CNTF 似乎没有明显作用。这一发现表明，常用于刺激脊髓损伤后轴突再生的某些神经营养因子也可能对内源性少突胶质细胞有有益的影响。
