Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Neurosci Res. 2009 Dec;65(4):393-401. doi: 10.1016/j.neures.2009.08.017. Epub 2009 Sep 8.
Trauma to the spinal cord initiates a series of cellular and biochemical processes that damage both neurons and glia. TGF-beta and its receptors are expressed around the injury site following a spinal cord injury. Here, we report that the intrathecal administration of a neutralizing antibody to TGF-beta1 in rats with thoracic spinal cord contusion results in a significant enhancement of the locomotor recovery. The inhibition of TGF-beta1 suppresses glial scar formation and upregulates microglia/macrophage activation after the injury, presumably providing a favorable environment for restoration of the neural network. Rats treated with the anti-TGF-beta1 antibody exhibited a mild enhancement of growth and/or preservation of axons in the injured spinal cord caudal to the site of contusion. These results support the possibility of using TGF-beta1 inhibitors in the treatment of human spinal cord injuries.
脊髓损伤会引发一系列细胞和生化过程，导致神经元和神经胶质细胞受损。TGF-β及其受体在脊髓损伤后会在损伤部位周围表达。在这里，我们报告在胸段脊髓挫伤的大鼠鞘内给予 TGF-β1 中和抗体可显著促进运动功能恢复。抑制 TGF-β1 可抑制神经胶质瘢痕形成，并上调损伤后小胶质细胞/巨噬细胞的激活，可能为神经网络的恢复提供有利的环境。用抗 TGF-β1 抗体治疗的大鼠在挫伤部位以下的损伤脊髓中观察到轴突的生长和/或保留有轻度增强。这些结果支持在人类脊髓损伤治疗中使用 TGF-β1 抑制剂的可能性。
