Studies on the mechanism of tissue repair and neural regenaration after brain injury

我们已经提出，在CNS损伤后的组织修复过程中形成的含有IV型胶原（Col IV）的纤维化瘢痕作为轴突再生的障碍。这一想法基于以下发现。(1)在7天大的新生小鼠中，其中横断的黑质纹状体多巴胺能（DA）轴突可以再生，在病变部位不形成纤维化瘢痕（Kawano，et.例如，2005年）的报告。(2)通过用Col IV合成的抑制剂2，2 '-联吡啶（DPY）处理来预防纤维化瘢痕形成促进了横断的黑质纹状体DA轴突的再生（Kawano，et.例如，在本研究中，（3）在下丘脑弓状核损伤后不形成纤维化瘢痕，其促进横断的NPY神经元的轴突再生（Homma，et.例如，（4）在经受降解CSPG的糖链的软骨素酶ABC（ChABC）处理的小鼠中消除了纤维化瘢痕，表明ChABC对轴突再生的促进作用是通过消除纤维化瘢痕介导的（Li，et.例如，在所有这些情况下，轴突再生发生在纤维化瘢痕未形成时，这强烈表明纤维化瘢痕是CNS损伤后轴突再生的主要障碍。

We have proposed that a fibrotic scar containing type IV collagen (Col IV) which is formed in the process of tissue repair after CNS injury acts as an impediment for axonal regeneration. This idea is based upon the following findings. (1) In 7-day-old newborn mice in which transected nigrostriatal dopaminergic (DA) axons can regenerate, the fibrotic scar is not formed in the lesion site (Kawano, et. al., 2005). (2) Prevention of fibrotic scar formation by treatment with 2, 2'-dipyridyl (DPY), an inhibitor of Col IV synthesis, promotes regeneration of transected nigrostriatal DA axons (Kawano, et. al., 2005).In the present studies, (3) the fibrotic scar is not formed after injury of the hypothalamic arcuate nucleus, which promotes axonal regeneration of transected NPY neurons (Homma, et. al., 2006) (4) The fibrotic scar is eliminated in mice subjected to chondroitinase ABC (ChABC) treatment which degraded glycochains of CSPGs, suggesting that the promoting effect of ChABC on axonal regeneration is mediated via the elimination of fibrotic scar (Li, et. al., 2007).In these all cases, the axonal regeneration occurs when the fibrotic scar is not formed, which strongly suggests that the fibrotic scar is a major impediment for axonal regeneration after CNS injury.