Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants
Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants
复制标题
纹状体内、黑质内和丘脑内核多巴胺能移植增强偏侧帕金森病大鼠的感觉运动行为恢复
作者：
K. Mukhida;K. Baker;D. Sadi;I. Mendez
影响帕金森病（PD）临床神经移植疗效的关键变量之一是最佳移植物放置位置。当前的移植范式侧重于将胎儿移植物异位放置在纹状体（ST）中，无法重建基底神经节回路或使重要基底神经节结构（例如黑质（SN）和丘脑底核（STN））中的神经元活动正常化。本研究的目的是通过评估 ST、SN 和 STN 中同时多巴胺能移植是否能诱导偏侧帕金森病大鼠的功能恢复，研究 PD 的多靶点神经移植策略。将46只黑质纹状体通路单侧6-羟基多巴胺损伤的雌性Wistar大鼠随机分为8组，仅接受损伤或在（1）ST、（2）SN、（3）STN、（4）ST和SN、（5）ST、SN和STN、（6）ST和STN或（7）SN和STN中接受仅损伤或注射900,000个胚胎大鼠腹侧中脑细胞。 STN。移植的细胞数量在移植部位之间平均分配。具有两个移植物的动物在每个结构中接受了450,000个细胞，而具有三个移植物的动物在每个结构中接受了300,000个细胞。通过安非他明诱导的旋转和踏步测试来评估恢复情况。使用酪氨酸羟化酶免疫组织化学评估移植物存活率。移植后 8 周，ST、SN 和 STN 中同时进行的多巴胺能移植导致旋转行为和迈步测试分数显着改善。纹状体内移植与旋转不对称性的显着恢复相关，而 SN 和 STN 移植与前肢功能评分的改善相关。这些结果表明，多个基底神经节目标（例如 ST 和 SN、或 ST 和 STN）的多巴胺能活性的恢复可促进复杂感觉运动行为的更完整的功能恢复。旨在优化基底神经节多巴胺能神经支配的多靶点移植策略可能对于改善帕金森病患者的临床结果至关重要。
One of the critical variables that influences the efficacy of clinical neural transplantation for Parkinson's disease (PD) is optimal graft placement. The current transplantation paradigm that focuses on ectopic placement of fetal grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or normalize neuronal activity in important basal ganglia structures, such as the substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study was to investigate a multitarget neural transplantation strategy for PD by assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were randomly divided into eight groups and received lesions only or injections of 900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN, (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number of cells transplanted was equally divided among grafting sites. Animals with two grafts received 450,000 cells in each structure, and animals with three grafts received 300,000 cells per structure. Recovery was assessed by amphetamine-induced rotations and the stepping tests. Graft survival was assessed using tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation, simultaneous dopaminergic transplants in the ST, SN, and STN induced significant improvement in rotational behavior and stepping test scores. Intrastriatal transplants were associated with significant recovery of rotational asymmetry, whereas SN and STN transplants were associated with improved forelimb function scores. These results suggest that restoration of dopaminergic activity to multiple basal ganglia targets, such as the ST and SN, or the ST and STN, promotes a more complete functional recovery of complex sensorimotor behaviors. A multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of the basal ganglia may be crucial in improving clinical outcomes in PD patients.
登录
查看更多内容
分离麻醉和纹状体神经元电生理学。
DOI：
10.1002/syn.890090111
发表时间：
1991
期刊：
Synapse (New York, N.Y.)
影响因子：
--
作者：
Kelland,MD;Chiodo,LA;Freeman,AS
通讯作者：
Freeman,AS
影响因子：
2.5
作者：
BERGMAN, H;WICHMANN, T;DELONG, MR
通讯作者：
DELONG, MR
影响因子：
158.5
作者：
KORDOWER, JH;FREEMAN, TB;OLANOW, CW
通讯作者：
OLANOW, CW
移植到哺乳动物中枢神经系统中。
影响因子：
33.6
作者：
Fisher,LJ;Gage,FH
通讯作者：
Gage,FH