Pavón-Fuentes N, Macías-González R, Blanco-Lezcano L, Alvarez-González L, Martínez-Martí L, Castillo-Díaz L, De La Cuétara Bernal K, Díaz C, Lorigados-Pedre L, Coro Y, García-Varona A Y, Rosillo J C, Díaz E
Centro Internacional de Restauración Neurológica (CIREN), La Habana, 11300, Cuba.
Rev Neurol. 2002;34(10):917-23.
The main strategy followed in neural transplants as a method of treatment for Parkinson s disease, both experimental and clinical, has been to introduce foetal mesencephalic cells into the target area: the striatum. However, when the dopaminergic cells in the substantia nigra degenerate, not only is the dopaminergic innervation of the striatum affected but also other nuclei: globus pallidus, substantia nigra, substantia nigra pars reticulata and subthalamic nucleus. A series of data from pharmacological and physiological studies offer strong evidence that the dopamine released in these nuclei may play an important role in regulating the output nuclei of the basal ganglia.
To evaluate the effect of transplanting foetal mesencephalic cells on the behaviour of 6 OH DA rats when introduced into the striatum and the subthalamic nucleus.
6 OH DA was used to induce lesions in the substantia nigra of rats, which were divided into several experimental groups. The rotating activity induced by D amphetamine (5 mg/kg, intraperitoneally) and apomorphine (0.05 mg/kg, subcutaneously) was evaluated before and three months after the transplant in all the experimental groups, except in the control group of healthy rats. The hemiparkinsonian rats received a total of 350,000 foetal ventral mesencephalic cells, which were implanted within small deposits in the striatum (8) and in the subthalamic nucleus (4).
Rotation induced by both drugs was significantly lower (p= 0.05) in animals that had had dopaminergic cells transplanted into the striatum body. No significant improvement in this behaviour was to be found when transplants were limited to just the subthalamus or, simultaneously, also to the striatum. A significant increase in rotating behaviour induced by apomorphine was observed in the group which received a transplant in just the subthalamus.
作为帕金森病治疗方法的神经移植,在实验和临床中所采用的主要策略是将胎儿中脑细胞引入目标区域:纹状体。然而,当黑质中的多巴胺能细胞发生退化时,不仅纹状体的多巴胺能神经支配会受到影响,其他核团也会受到影响,如苍白球、黑质、黑质网状部和丘脑底核。一系列药理和生理研究数据提供了有力证据,表明在这些核团中释放的多巴胺可能在调节基底神经节的输出核团方面发挥重要作用。
评估将胎儿中脑细胞分别移植到纹状体和丘脑底核后对6-OH DA大鼠行为的影响。
使用6-OH DA诱导大鼠黑质损伤,将大鼠分为几个实验组。除健康大鼠对照组外,在所有实验组中,于移植前及移植后三个月评估由右旋苯丙胺(5毫克/千克,腹腔注射)和阿扑吗啡(0.05毫克/千克,皮下注射)诱导的旋转活动。半帕金森病大鼠共接受350,000个胎儿腹侧中脑细胞,这些细胞被植入纹状体(8个)和丘脑底核(4个)的小沉积部位。
将多巴胺能细胞移植到纹状体主体的动物中,两种药物诱导的旋转明显降低(p = 0.05)。当移植仅限于丘脑底核或同时也移植到纹状体时,未发现这种行为有明显改善。仅在丘脑底核接受移植的组中,观察到阿扑吗啡诱导的旋转行为显著增加。