REGENERATIVE REMODELING OF SPINAL ARCHITECTURE

本项目旨在测试以下假设： 周围神经横断会导致信息中断 外围目标，进而导致： 1. 向 DRG 细胞发出信号； 一个。上调生长所需的蛋白质和细胞骨架元素 中央和外周轴突的生长锥形成（启动）， b.从突触后撤回中央细初级传入神经末梢 目标。 2. 空缺突触位点与准备生长的 DRG 细胞的结合 导致第一层和第二层的中央发芽和新突触发生。 3. 由此产生的某些重新连接可能不合适，这可能会导致 帮助解释有时会导致的异常敏感和疼痛 这个病变。 支持初步证据的是，在叶片中发现了生长锥 I 和 II 在坐骨神经横断后 2 周内，有很多轴突，但是 此时 I 和 II 层中几乎没有突触被 GAP-43 标记 并且在许多研究中发现了精细初级传入神经的直接染色 操作侧面积更宽。 如果有进一步的证据证实上述假设，则重大意义 背角突触结构的重塑是 主要是一个主动的过程。 这个过程并不完美 可能是有时会出现异常感觉状态的一个因素 周围神经横断。 最终的希望是，如果这种活动 重塑可以被量化并因此被理解，它可以被操纵 人类苦难的利益。

The present project is designed to test the following hypotheses: That peripheral nerve transection leads to disruption of information from peripheral targets, which in turn leads to: 1. A signal to DRG cells to; a. upregulate growth proteins and cytoskeletal elements necessary for growth cone formation (priming) in both central and peripheral axons, b. withdraw the central fine primary afferent terminals from postsynaptic targets. 2. The combination of vacant synaptic sites and DRG cells primed for growth leads to central sprouting and neosynaptogenesis in lamina I and II. 3. Some of the resulting reconnections may be inappropriate and this could help explain the abnormal sensibility and pain that sometimes results from this lesion. Supporting preliminary evidence is that growth cones are found in laminae I and II within 2 weeks of sciatic nerve transection, that many axons but almost no synapses are labeled with GAP-43 in laminae I and II at this time and that direct staining of fine primary afferents is found over a much wider area on the operated side. If further evidence confirms the above hypotheses, the major significance will be that the remodeling of dorsal horn synaptic architecture is primarily an active process. That this process is not perfect is presumably a factor in the abnormal sensory states that sometimes follow peripheral nerve transection. The ultimate hope is that, if this active remodeling can be quantified and thus understood, it can be manipulated for the benefit of human suffering.