Investigation of neuroprotctive effect of glial cell line-derived neurotrophic factor in neonatal central and peripheral nervous system

胶质细胞源性神经营养因子对新生儿中枢和周围神经系统神经保护作用的研究

• 批准号: 14370535
• 负责人: IKENOUE Tsuyomu
• 金额: $ 6.66万
• 依托单位: (Miyazaki Medical College) University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370535/
• 关键词: Glial cell line-derived neurotrophic factor; Neonate; Fetus; Hypoxia-icchemia; Free radical; Edaravone; Erb's palsy; Slowly progressive brain damage; グリア細胞株由来神経栄養因; 脳脊髄液

(A)We examined the effect of Glial cell line-derived neurotrophic factor (GDNF), newly discovered neuroprotective neurotrophin in neonatal rat model.1)We have shown that the infarction is reduced by direct injection of GDNF immediately after the hypoxic-ischemic insult. For the purpose of clinical application, we developed a delivery system, which enabled the constant supply of GDNF to the brain. Encapsulated GDNF-secreting cells, which was produced with bioengineering technique, was implanted 48hrs prior to hypoxic-ischemic insult. The GDNF capsule significantly reduced the infarction volume in the brain of neonatal hypoxic-ischemic encephalopathy rat model.2)Local administration of GDNF in a neonatal preganglionic Erb's palsy model resulted in significant improvement in deficits on the basis of behavioral and histological evaluations.(B)A newly developed free radical scavenger, edaravone, which is commonly used as the first choice of drug for adult cerebral ischemia, was examined for … More the ability of neuroprotection in neonatal rat model of hypoxic-ischemic encephalopathy.1)The optimal duration of edaravone administration at the dosage of 9mg/kg was evaluated in terms of histological and behavioral improvement. Acute (2 and 5 days) edaravone therapy has greater effect on neonatal hypoxic-ischemic brain damage than that of chronic (10 days) therapy.2)Edaravone significantly decreased the production of reactive oxygen radicals in the neonatal examined with microdialysis method during hypoxic-ischemic stress.3)In the neonatal hypoxic-ischemic encephalopathy model, edaravone-treated rat group showed the ability to reduce nitroxide radical even in the contralateral hemisphere at the age of 6 wk.(C)Long-term follow up study of an unilateral hypoxic-ischemic encephalopathy rat model revealed compensative hypertrophy of the contralateral brain hemisphere which was observed within 5 wks after the insult. The volume of the both hemispheres were gradually decreased subsequently. We named this phenomenon as "slowly progressive brain damage". Less

(A)我们检测了神经胶质细胞系来源的神经营养因子（GDNF），新发现的神经保护神经营养因子在新生大鼠模型中的作用。1)我们已经证明，在缺氧缺血性损伤后立即直接注射GDNF可减少梗死。为了临床应用，我们开发了一种输送系统，使GDNF能够持续供应到大脑。用生物工程技术制备的囊化gdnf分泌细胞，在缺氧缺血性损伤48小时前植入。GDNF胶囊可显著减少新生儿缺氧缺血性脑病模型大鼠脑梗死体积。2)在新生儿神经节前Erb麻痹模型中局部给予GDNF，在行为学和组织学评估的基础上显著改善了缺陷。(B)新研制的自由基清除剂依达拉奉是治疗成人脑缺血的首选药物，在新生儿大鼠缺氧缺血性脑病模型中检测其神经保护能力。1)从组织学和行为改善方面评价依达拉奉9mg/kg给药时间的最佳选择。急性（2天和5天）依达拉奉治疗对新生儿缺氧缺血性脑损伤的影响大于慢性（10天）治疗。2)依达拉奉可显著降低微透析新生儿缺氧缺血性应激时活性氧自由基的产生。3)在新生儿缺氧缺血性脑病模型中，依达拉奉治疗组大鼠在6周龄时甚至在对侧半球也显示出减少一氧化氮自由基的能力。(C)单侧缺氧缺血性脑病大鼠模型的长期随访研究显示，在损伤后5周内观察到对侧脑半球代偿性肥大。随后，双脑体积逐渐减小。我们将这种现象命名为“缓慢进行性脑损伤”。少

项目成果

Yi Xin Xia, et al.: "Cerebral blood flow distribution and hypoxic-ischemic brain damage in newborn rats"J. Obstet. Gynaecol. Res.. 28・6. 320-326 (2002)

Yi Xin Xia 等：“新生大鼠的脑血流分布和缺氧缺血性脑损伤”J. Obstet. 28・6 (2002)。

Ikeda T, Xia YX, Kaneko M, Sameshima H, Ikenoue T: "Effect of the free radical scavenger, 3-methyl-1-2pyrazolin-5-one (MCI-186), on hypoxia-ischemia-induced brain injury in neonatal rats"Neuroscience Letters. 329. 33-36 (2002)

Ikeda T、Xia YX、Kaneko M、Sameshima H、Ikenoue T：“自由基清除剂 3-甲基-1-2吡唑啉-5-酮 (MCI-186) 对新生儿缺氧缺血性脑损伤的影响

Tomoaki Ikeda, et al.: "Dexamethasone prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats"Behavioural Brain Research. 136. 161-170 (2002)

Tomoaki Ikeda 等人：“地塞米松可预防大鼠新生儿缺氧缺血性脑损伤后的长期学习障碍”行为脑研究。

Tomoaki Ikeda, et al.: "Effect of the free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), on hypoxia-ischemia-induced brain injury in neonatal rats"Neuroscience Letters. 329. 33-36 (2002)

Tomoaki Ikeda 等人：“自由基清除剂 3-甲基-1-苯基-2-吡唑啉-5-酮 (MCI-186) 对新生大鼠缺氧缺血性脑损伤的影响”神经科学快报

Ikeda T, Mishima K, Yoshikawa T, Iwasaki K, Fujiwara M, Xia YX, Ikenoue T: "Dexamethasone prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats"Behavioural Brain Research. 136. 161-170 (2002)

Ikeda T、Mishima K、Yoshikawa T、Iwasaki K、Fujiwara M、Xia YX、Ikenoue T：“地塞米松可预防大鼠新生儿缺氧缺血性脑损伤后的长期学习障碍”行为脑研究。