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

脑损伤后组织修复和神经再生机制研究

• 批准号: 18500271
• 负责人: KAWANO Hitoshi
• 金额: $ 2.5万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500271/
• 关键词: mouse brain; injury; neural regeneration; glial scar; proteoglycan; fibrotic scar; hypothalamus; teissue repair; 脳; ドーパミン神経路; 細胞移植; 嗅球グリア; 繊維芽細胞; 瘢痕; コラーゲン; マウス; コンドロイチン硫酸; 弓状核

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.

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）。(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。

项目成果

Central nervous system injury and chondroitin sulfate proteoglycans, In Neural Proteoglycans

中枢神经系统损伤和硫酸软骨素蛋白多糖，神经蛋白多糖

• 发表时间: 2007
• 期刊: Research Signpost, Kerala, India
• 作者: Teng X;Nagata I;Li H-P;Kimura-Kuroda J;Sango K;Kawamura K;Raisman G;Kawano H;Kawano H
• 通讯作者: Kawano H

Regeneration of nigrostriatal dopaminergic axons after transplantation of olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation in the lesion site.

嗅鞘细胞和成纤维细胞移植后黑质纹状体多巴胺能轴突的再生可防止病变部位纤维化疤痕的形成。

• 发表时间: 2008
• 期刊: Journal of Neuroscience Research (印刷中)
• 作者: Teng X;Nagata I;Li H-P;Kimura-Kuroda J;Sango K;Kawamura K;Raisman G;Kawano H
• 通讯作者: Kawano H

Regeneration of mgrostriatal dopaminergic axons after transplantation of olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation in the lesion site

嗅鞘细胞和成纤维细胞移植后下颌纹状体多巴胺能轴突的再生可防止病变部位纤维化疤痕的形成

• 发表时间: 2008
• 期刊: J. Neurosci. Res. (in press)
• 作者: Teng X

Regeneration of nigrostriatal dopaminergic axons by degradation of chondroitin sulfate is accompanied by elimination of the fibrotic scar and glia limitans in the lesion site

通过硫酸软骨素的降解实现黑质纹状体多巴胺能轴突的再生，同时消除病变部位的纤维化疤痕和神经胶质细胞界限

• DOI: 10.1002/jnr.21141
• 发表时间: 2007-02-15
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Li, Hong-Peng;Homma, Akiko;Kawano, Hitoshi
• 通讯作者: Kawano, Hitoshi

Neural Proteoglycans

神经蛋白多糖

• 发表时间: 2007
• 作者: Masu M.;et. al.
• 通讯作者: et. al.