The role of cell adhesion molecules and neurotrophic factors in reconstruction of nociceptive pathways in spinal cord and brainstem after peripheralaxotomy

细胞粘附分子和神经营养因子在外周轴切断术后脊髓和脑干伤害感受通路重建中的作用

• 批准号: 11671360
• 负责人: HASEGAWA Mitsuhiro
• 金额: $ 2.3万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671360/
• 关键词: nerve regeneration; allodynia; Rexed II; spinalcord; E-cadherin; qalectin-1; substance-P; catenins; regeneration; subsauce-P

The ultimate aim of this study is to know the plasticity of primary sensory pathways, especially pain sensation in the spinal cord, resulting in allodynia, hyperalgesia, and persistent pain to the patients. To examine this, the effects of peripheral axotomy to the alteration of the expression of E-cadherin which is exclusively expressed inlamina II of Rexed in the spinal cord dorsal horn was firstly analysed. This expression tem porarily disappeared by day 7 after axotomy and reappeared following partial axonal regeneration on day 63. In contrast, it remained undetectable following complete nerve degeneration. Cadherin-associated protein, catenins are also examined. Administration of NGF rescued the immunoreactivity of substance P, which is known to disappear after peripheral axotomy, but not influence that of both E-cadherin and alpha N-catenin. Secondly, to investigate the detailed cellular effects of oxidized galectin-1, which effect to nerve regeneration has been recently identified, acellular auto- and allograft model were utilized. Our results indicated that local application of exogenous rhGal-1/Ox promotes the migration of Schwann cells followed by axonal regeneration from both motor and sensory neurons, and that Gal-1/Ox is a key factor of initial stage of neuronal regeneration. These models would be utilized for further investigation of the plasticity of primary sensory pathways.

本研究的最终目的是了解初级感觉通路的可塑性，特别是脊髓的痛觉，导致异常性疼痛，痛觉过敏和持续性疼痛的患者。为了验证这一点，首先分析了外周轴突切断对脊髓背角Rexed II层中唯一表达的E-cadherin表达变化的影响。这种表达在轴突切断后第7天暂时消失，并在第63天部分轴突再生后再次出现。相反，在完全神经变性后，它仍然检测不到。还检查了钙粘蛋白相关蛋白、连环蛋白。神经生长因子的管理挽救了P物质的免疫反应性，这是已知的外周神经切断后消失，但不影响E-钙粘蛋白和α N-连环蛋白。其次，为了研究氧化半乳糖凝集素-1对神经再生的影响，最近已经确定了氧化半乳糖凝集素-1对神经再生的影响，使用了脱细胞自体和同种异体移植模型。我们的研究结果表明，局部应用外源性rhGal-1/Ox促进雪旺细胞的迁移，随后由运动和感觉神经元的轴突再生，并且Gal-1/Ox是神经元再生的初始阶段的关键因素。这些模型将用于进一步研究初级感觉通路的可塑性。