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

(A)我们研究了新发现的神经保护神经营养因子--胶质细胞源性神经营养因子(GDNF)在新生大鼠模型中的作用。1)我们已经证明，在缺氧缺血后立即直接注射GDNF可以减少脑梗塞。为了临床应用的目的，我们开发了一种给药系统，使GDNF能够持续地供应到大脑。用生物工程技术制备微囊化GDNF分泌细胞，在缺氧缺血性损伤前48小时植入。2)在新生神经节前Erb‘s麻痹模型中，局部应用GDNF可在行为学和组织学评估的基础上显著改善缺陷。(B)对新开发的自由基清除剂依达拉奉进行…检查，该药通常被用作治疗成人脑缺血的首选药物对新生大鼠缺氧缺血性脑病模型的神经保护作用更强。1)从组织学和行为学的角度评价依达拉奉9 mg/kg给药的最佳时间。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)依达拉奉显著降低新生儿缺氧缺血性脑病模型中微透析法检查的新生儿脑组织中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出生6周时，即使是对侧大脑半球，依达拉奉治疗组也表现出降低一氧化氮自由基的能力。(C)对单侧缺氧缺血性脑病大鼠模型的长期随访研究显示，损伤后5周内出现对侧大脑半球代偿性肥大。随后，双侧大脑半球的体积逐渐减小。我们将这种现象命名为“缓慢进行性脑损伤”。较少

(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