Liu D M, Lin S Z, Wang S D, Wu M Y, Wang Y
Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Cell Transplant. 1999 Nov-Dec;8(6):583-91. doi: 10.1177/096368979900800604.
Previous studies have suggested that allografting peripheral sympathetic ganglia, such as superior cervical ganglia, partially relieves clinical or behavioral deficits in parkinsonian patients and animals. However, removal of these ganglia can cause Homer's syndrome, which limits the utilization of this approach. Hyperhidrosis, a disease of excessive sweating, is commonly seen in young Orientals. Treatment of hyperhidrosis often involves surgical removal of the second thoracic sympathetic ganglia (T2G), which contain catecholaminergic neurons. The purpose of our study was to investigate behavioral responses and tyrosine hydroxylase (TH) immunoreactivity in hemiparkinsonian rats at different time points after transplantation of human T2G from hyperhidrotic patients. Athymic Fisher 344 rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle to destroy the nigrostriatal dopaminergic (DA) pathway. The effectiveness of lesions was tested by measuring methamphetamine (MA)-induced rotations. These unilaterally lesioned rats were later transplanted with T2G or T2 fiber tract (T2F) obtained from adult hyperhidrotic patients. Animals grafted with T2G showed a reduction in MA-induced rotation by 2 weeks; however, rotation returned to the pregrafting levels by 3 months. Animals receiving T2F grafts did not show any reduction of rotation over a 3-month period. Animals were later sacrificed for TH immunostaining at different time points. Tyrosine hydroxylase-positive [TH(+)] cell bodies and fibers were found in the lesioned striatum 2-4 weeks after T2G grafting, suggesting the survival of transplants. Two to 3 months after grafting, TH(+) fibers were still found in almost all the recipients. However, TH(+) cell bodies were found in only three of seven rats studied. Animals receiving T2F grafting did not show any TH immunoreactivity in the lesioned striatum over the 3-month period. These data indicate that T2G transplants from adult hyperhidrotic patients can survive and provide transient normalization of the motor behavior in the hemiparkinsonian athymic rats. Because of the short-term improvement in behavior after grafting, the use of T2G in human trials should be cautious at the present time. Further laboratory research is required.
先前的研究表明,同种异体移植外周交感神经节,如颈上神经节,可部分缓解帕金森病患者和动物的临床或行为缺陷。然而,切除这些神经节会导致霍纳综合征,这限制了该方法的应用。多汗症是一种出汗过多的疾病,常见于年轻的东方人。多汗症的治疗通常涉及手术切除第二胸交感神经节(T2G),该神经节含有儿茶酚胺能神经元。我们研究的目的是调查来自多汗症患者的人T2G移植后不同时间点半帕金森病大鼠的行为反应和酪氨酸羟化酶(TH)免疫反应性。无胸腺Fisher 344大鼠单侧注射6-羟基多巴胺至内侧前脑束以破坏黑质纹状体多巴胺能(DA)通路。通过测量甲基苯丙胺(MA)诱导的旋转来测试损伤的有效性。这些单侧损伤的大鼠随后移植了从成年多汗症患者获得的T2G或T2纤维束(T2F)。移植T2G的动物在2周时MA诱导的旋转减少;然而,到3个月时旋转恢复到移植前水平。接受T2F移植的动物在3个月期间旋转没有任何减少。随后在不同时间点处死动物进行TH免疫染色。T2G移植后2-4周,在损伤的纹状体中发现酪氨酸羟化酶阳性[TH(+)]细胞体和纤维,表明移植存活。移植后2至3个月,几乎所有接受者中仍发现TH(+)纤维。然而,在研究的7只大鼠中,只有3只发现了TH(+)细胞体。接受T2F移植的动物在3个月期间损伤的纹状体中未显示任何TH免疫反应性。这些数据表明,来自成年多汗症患者的T2G移植能够存活,并使半帕金森病无胸腺大鼠的运动行为暂时恢复正常。由于移植后行为有短期改善,目前在人体试验中使用T2G应谨慎。需要进一步的实验室研究。