A mechanism of retrograde degeneration and preservation of the facial nucleus following axotomy in brainstem

脑干轴突切除术后面核逆行变性和保存机制

• 批准号: 16591434
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591434/
• 关键词: facial nucleus; retrograde degeneration; erythropoietin; nitrite oxide; brainstem; NADPH; facial nerve injury; Schwann cell; stereotactic operation; axotomy; autograft; erythropoietin; striate muscle; sciatic nerve; neuronal cell death

This study was aimed to find out whether recombinant human erythropoietin (rhEPO) might have neuroprotective effect on the lesioned facial nucleus after axotomy of the central portion in brain stem. In the facial nerve transection in brain stem, compared with the control side, the survival ratio of the facial motoneurons was 25.0±2.4% (175±18.4/703±37.1) on day 14 and 2.8±1.4%(22.3±12.7/783±58.5) on day 28. Immunohistochemically, EPO were detected on astrocyte and EPO-R were detected on facial motoneurons in control. EPO expression was localized to reactive astrocytes in lesioned side on day 14. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry to detect the neuronal nitric oxide synthase (nNOS) showed that the facial motoneurons were not positive for NADPH-d in control and on day 1. On the contrary, increased NADPH-d activity was seen in the facial motoneurons on day 4. The number of NADPH-d positive neurons and the intensity increased along with survival time, and nearly all survived motoneurons were stained on day 14. Administration of rhEPO (5000 U/kg) decreases the enzymatic expression of the number and staining intensity on day14(75.3±4.9%(481±128/636±144). The rats received rhEPO daily at dose of 5000 U/kg showed the 42.6±6.7% of the survival ratio of facial motoneurons on day 14, and 8.2±0.5%(57.3±11.2/703±145) on day 28. On the basis of these findings, it is suggested that rhEPO could act as one of the neuroprotective factors either by suppressing the nNOS activity or reducing the NO-mediated neurotoxicity in the lesioned motoneurons.

本研究旨在探讨重组人促红细胞生成素（rhEPO）是否对脑干中枢性神经切开术后受损面神经核具有神经保护作用。在脑干面神经横断组中，与对照组相比，第14天面部运动神经元存活率为25.0±2.4%(175±18.4/703±37.1)，第28天存活率为2.8±1.4%（22.3±12.7/783±58.5）。免疫组织化学检测，星形胶质细胞和对照组面部运动神经元均检测到EPO- r。第14天，EPO表达局限于病变侧的反应性星形胶质细胞。烟酰胺腺嘌呤二核苷酸磷酸二氢酶（NADPH-d）组织化学检测神经元一氧化氮合酶（nNOS）显示对照组和第1天面部运动神经元NADPH-d不阳性。相反，第4天面部运动神经元中NADPH-d活性增加。NADPH-d阳性神经元的数量和强度随存活时间的延长而增加，在第14天几乎所有存活的运动神经元都染色。rhEPO （5000 U/kg）使第14天的酶表达数和染色强度降低75.3±4.9%（481±128/636±144）。每天给药5000 U/kg的大鼠，第14天面部运动神经元存活率为42.6±6.7%，第28天存活率为8.2±0.5%（57.3±11.2/703±145）。由此可见，rhEPO可能通过抑制nNOS活性或减轻no介导的神经毒性而发挥神经保护因子的作用。