Azari Michael F, Profyris Christos, Karnezis Tara, Bernard Claude C, Small David H, Cheema Surindar S, Ozturk Ezgi, Hatzinisiriou Irene, Petratos Steven
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
J Neuropathol Exp Neurol. 2006 Sep;65(9):914-29. doi: 10.1097/01.jnen.0000235855.77716.25.
As a consequence of secondary pathophysiological mechanisms elicited after spinal cord injury (SCI), oligodendrocytes die by waves of apoptosis. This ultimately results in demyelination of intact axons leading to a loss of their conducting properties. Preservation of as few as 5% to 10% of myelinated axons in individual tracts can confer locomotor recovery. Thus, strategies aimed at rescuing mature oligodendrocytes ensheathing viable axons are likely to be of therapeutic significance. We report that leukemia inhibitory factor (LIF) can prevent oligodendrocyte apoptosis, notably contralateral to the spinal cord lesion, through the induction of the JAK/STAT and Akt signaling pathways as well as by potentiating the expression of the antiapoptotic molecule, cIAP2. Reduced oligodendrocyte apoptosis after SCI with LIF administration resulted in a substantial decrease in demyelination shown by the preservation of lamellated myelin surrounding viable axons and deposition of the degraded myelin basic protein. The data suggest that LIF signals survival in oligodendrocytes after SCI, prevents the secondary wave of demyelination, and thereby reduces inhibitory myelin deposits.
由于脊髓损伤（SCI）后引发的继发性病理生理机制，少突胶质细胞会因凋亡浪潮而死亡。这最终导致完整轴突的脱髓鞘，使其传导特性丧失。在各个神经束中，仅保留5%至10%的有髓轴突就能实现运动功能恢复。因此，旨在挽救包裹着存活轴突的成熟少突胶质细胞的策略可能具有治疗意义。我们报告称，白血病抑制因子（LIF）可通过诱导JAK/STAT和Akt信号通路以及增强抗凋亡分子cIAP2的表达，预防少突胶质细胞凋亡，尤其是在脊髓损伤对侧。给予LIF后，SCI后少突胶质细胞凋亡减少，导致脱髓鞘现象大幅减少，表现为存活轴突周围板层状髓鞘的保留以及降解的髓鞘碱性蛋白的沉积。数据表明，LIF在SCI后为少突胶质细胞提供存活信号，防止继发性脱髓鞘浪潮，从而减少抑制性髓鞘沉积物。
