ENDOGENOUS REPAIR MECHANISMS AFTER SPINAL CORD INJURY

脊髓损伤（SCI）的最终功能结局是继发性退行性事件和内源性修复机制相互作用的结果。我们现在知道，继发性损伤过程包括诱导胶质细胞和神经元的程序性细胞死亡。我们也知道脊髓损伤后有大量的修复事件涉及生长和营养因子。关于中枢神经系统损伤后刺激增殖祖细胞的令人兴奋的新信息表明，可能比以前想象的更多的修复。我们已经开发了大鼠挫伤脊髓损伤模型，以模仿人类脊髓损伤的一些临床特征。面对持续的凋亡细胞死亡，恢复会随着时间的推移而发生。与此同时，室管膜区细胞以及白色细胞增生，似乎有助于病变边缘的修复。此外，可以看到新的轴突生长进入病变区域。以这些观察结果为背景，我们将研究甲基强的松龙（MP）和碱性成纤维细胞生长因子（bFGF）对脊髓损伤后这些细胞事件的影响。MP是目前临床治疗急性脊髓损伤的黄金标准，但其作用机制尚不完全清楚。BFGF是一种很有前景的治疗脑和脊髓损伤的方法，它可能延缓细胞凋亡并促进中枢神经系统祖细胞的细胞增殖。我们将使用既定的行为方法研究挫伤和背半球脊髓损伤后MP和bFGF的功能恢复和作用。我们将研究这些药物对神经元和神经胶质细胞凋亡的影响，以及对细胞增殖和表型表达的影响。我们将研究联合治疗对行为和皮质脊髓束再生的影响，这将是这两种病变类型轴突生长的晴雨表。该结果有望为脊髓损伤的生物学提供进一步的信息，并评估可能在短时间内进入临床的潜在治疗方法。

The final functional outcome of spinal cord injury (SCI) is the result of an interplay between secondary degenerative events and endogenous mechanisms of repair. We now know that the secondary injury process includes the induction of programmed cell death in both glia and neurons. We also know that there are substantial reparative events in the cord after injury that involve growth and trophic factors. Exciting new information on the stimulation of proliferating progenitor cells after injury to the CNS suggest that more repair may be possible than previously imagined. We have developed models of contusion spinal cord injury in rats that mimic some of the clinical features of SCI in man. Recovery occurs over time in the face of continuing apoptotic cell death. At the same time, ependymal zone cells as well as cells in the white proliferate and appear to contribute to repair at the lesion margins. In addition, new axonal growth can be seen entering the lesion area. Using these observations as a background, we will examine the effects of methylprednisolone (MP) and basic fibroblast growth factor (bFGF) on these cellular events after SCI. MP is the current Agold standard@ of clinical treatment of acute SCI, but its mechanisms of action are not fully understood. BFGF is a promising treatment for brain and spinal trauma that is likely to retard apoptosis and drive cellular proliferation of CNS progenitor cells. We will study recovery of function and the effects of MP and bFGF after both contusion and dorsal hemisection SCI using established behavior methods. We will examine the effect of these agents on apoptotic cell death of neurons and glia, and on cell proliferation and phenotypic expression. We will examine the effects of combination treatments on behavior and the regeneration of the corticospinal tract, which will be used a barometer of axonal growth in these two lesion types. The results are expected to provide further information on the biology of SCI as well as an assessment of potential therapies that could reach the clinic in a short time.