REGENERATIVE REMODELING OF SPINAL ARCHITECTURE

本项目旨在检验以下假设： 周围神经切断会导致信息中断 外围目标，这反过来又导致： 1.给DRG细胞的信号; a.上调生长蛋白和细胞骨架元素， 在中央和外周轴突中的生长锥形成（引发）， B.从突触后回撤中枢精细初级传入终末 目标的 2.空的突触部位和准备生长的DRG细胞的结合 导致板层I和II中的中央发芽和新突触发生。 3.一些由此产生的重新连接可能是不适当的，这可能 有助于解释异常的敏感性和疼痛，有时导致 这个病变。 初步的证据是在纹层中发现了生长锥 I和II在坐骨神经切断后2周内，轴突数量较多，但 此时，在板层I和II中几乎没有突触被GAP-43标记 而且，在很长一段时间内， 操作侧的区域更宽。 如果进一步的证据证实了上述假设， 背角突触结构的重塑 主要是一个积极的过程。 这个过程并不完美， 这可能是导致异常感觉状态的一个因素 周围神经横断 最终的希望是，如果这个活跃的 重塑可以量化，因此可以理解，它可以被操纵， 人类苦难的好处。

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.