BRAIN TRANSPLANT TREATMENT FOR PARKINSONIANS

胎鼠黑质纹状体内移植的实验研究 多巴胺输入的失神经化已经成功地恢复了 一些运动行为。 新发现灵长类动物可以 用甲基苯基四氢吡啶使他患上了帕金森病 （MPTP）使得将胎儿移植治疗扩展到 灵长类动物 我们将训练雄性邦尼特猴（Macaca radiata） 用左手或右手拉动杠杆来获取食物 奖励 一个灯光提示将被用来指示使用哪只手 为了赏金 在达到稳定性能后，动物 每天注射MPTP 0.5 mg/kg I.M. 平均需要4至5次注射。 动物在急性中毒期间将被饲养 如果有必要的话，可以用管饲。 动物中 自发从病变中恢复，额外疗程 将给予MPTP，直到出现显著和稳定的病变结果。 一旦达到稳定的性能（3 - 4个月后， 诱导综合征），动物将被移植 来自胎儿Bonnet腹侧中脑的胎儿组织 猴胚胎期35 - 40天。 注射切碎的组织 单侧进入尾状核头部和壳核 在多个地点。 动物将每周检测两次 间隔，以改善电机性能。 我们预计， 肢体的运动性能会有更大的改善， 移植部位的对侧，发生在移植后3至4个月 移植手术 动物将在术后6个月处死 用酪氨酸羟化酶研究移植物和脑 移植证据免疫细胞化学技术 生存 在随后的实验中，动物将被移植到 只进入尾状核或壳核，看看哪个部位更重要 来改善运动机能 延迟匹配样本测试将 在后面的实验中评估更高的认知技能。 这些实验的结果将直接预测 帕金森病患者的胚胎移植。

Transplantation of rat fetal substantial nigra into rat striatum denervated of dopamine input has been successful at restoring some motor behaviors. The new discovery that primates can be made Parkinsonian with the drug methylphenyltetrahydropyridine (MPTP) has made it possible to extend fetal transplant therapy to the primate. We will train male Bonnet (Macaca radiata) monkeys to pull a lever with either the left or right hands for a food reward. A light cue will be used to signal which hand is to be used for the reward. After stable performance is achieved, animals will be made Parkinsonian with daily injections of MPTP 0.5 mg/kg i.m. An average of 4 to 5 injections will be required. Animals will be maintained during the acute intoxication syndrome with tube feedings if necessary. In animals spontaneously recovering from the lesion, additional courses of MPTP will be given until a significant and stable lesion results. Once stable performance is achieved (3-4 months after the induction of the syndrome), animals will be transplanted with fetal tissue from the ventral mesencephalon of fetal Bonnet monkeys embryonic age 35-40 days. Injections of minced tissue will be made unilaterally into head of caudate and into putamen at multiple sites. Animals will be tested at twice weekly intervals for improved motor performance. We expect that there will be greater improvement in motor performance in the limb contralateral to the transplant site occurring 3 to 4 months after the transplant. Animals will be sacrificed 6 months after transplant and brain studied with tyrosine hydroxylase immunocytochemical techniques for evidence of transplant survival. In subsequent experiments, animals will be transplanted only into caudate or putamen to see which site is more important for motor improvement. Delayed match to sample tests will be done to assess higher cognitive skills in these later experiments. The outcome of these experiments will directly predict the value of fetal transplate in human patients with Parkinson's disease.