REGENERATIVE REMODELING OF SPINAL ARCHITECTURE

本项目旨在检验以下假设： 外周神经切断会导致信息中断 外围目标，进而导致： 1.向DRG细胞发出信号； A.上调生长蛋白和细胞骨架元素 中央轴突和外周轴突的生长锥体形成(启动)， B.从突触后取出中央细小初级传入终末 目标。 2.空白突触部位和准备生长的背根节细胞的组合 导致板层I和II的中心萌发和新突触的形成。 3.由此产生的一些重新连接可能是不适当的，这可能 帮助解释有时由以下原因引起的异常敏感和疼痛 这个损伤。 支持初步证据的是在叶片中发现了生长锥体。 I和II在坐骨神经切断后2周内，有那么多轴突，但 目前，在板层I和II中几乎没有突触被GAP-43标记 而细小的初级传入神经的直接染色在许多情况下都可以发现 手术侧的面积更大。 如果进一步的证据证实了上述假设，重大意义 将是背角突触结构的重塑 主要是一个积极的过程。这一过程并不完美 可能是导致异常感觉状态的一个因素 周围神经横断术。最终的希望是，如果这一活动活跃 重塑是可以量化的，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.