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,二次损伤过程包括程序性细胞死亡的诱导神经元和神经胶质。我们也知道有大量的赔偿的事件绳受伤后,包括增长和营养因素。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。同时,室管膜区细胞以及细胞在白色的增殖和似乎有助于修复损伤的利润率。此外,可以看到新的轴突生长进入病变区域。使用这些观察作为背景,我们将检查的影响甲基强的松龙(MP)和基本的纤维母细胞生长因子(bFGF) SCI后这些细胞的事件。议员是当前Agold standard@临床治疗急性SCI,但它的作用机理还没有完全理解。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。我们将研究恢复功能和议员的影响和bFGF挫伤和背侧半切术SCI后使用行为建立方法。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。我们将检查联合治疗的影响行为和皮质脊髓束的再生,将使用一个轴突生长在这两个病变类型的晴雨表。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.