Pallini R, Fernandez E, Lauretti L, Dell'Anna E, La Marca F, Gangitano C, DelFà A, Olivieri-Sangiacomo C, Sbriccoli A, Rossi G F
Center for Regeneration in the Nervous System, Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy.
J Neurosurg. 1996 Mar;84(3):487-93. doi: 10.3171/jns.1996.84.3.0487.
The superior cervical ganglion (SCG) has been grafted to the brain of adult rats in an attempt to reverse the parkinsonian syndrome that follows destruction of central dopamine systems. However, the main limitation to this approach is the massive cell death that occurs in the grafted SCG after direct transplantation into the brain. In adult rats, 6-hydroxydopamine (6-OHDA) was stereotactically injected into the right substantia nigra (SN). One month later, dopamine denervation was assessed using the apomorphine-induced rotational test. In rats with a positive test, an autologous peripheral nerve (PN) graft was tunneled from the right cervical region to the ipsilateral parietal cortex. One end of PN graft was sutured to the transected postganglionic branch of the SCG and the other end was inserted into a surgically created cortical cavity. The apomorphine test was repeated at 3 days and again at 1, 3, and 5 months after surgery. The brain, SCG, and PN graft were studied under light and electron microscopy and with the tyrosine hydroxylase immunohistochemical and horseradish peroxidase tracing methods. Three days after grafting, there were no significant differences on the apomorphine test as compared to the preoperative test. Conversely, 1,3, and 5 months after grafting, the number of rotations was reduced by 69% (+/-20.2), 66.6% (+/-17.1), and 72.5% (+/-11.3), respectively. Control rats that received a free PN graft to the brain and underwent section of the postganglionic branch of the SCG did not show significant changes on the apomorphine test after surgery. Histological examination revealed that the PN graft was mostly reinnervated by amyelinic axons of small caliber. Approximately 40% of the SCG neuronal population that normally projects to the postganglionic branch survived axotomy and regenerated the transected axons into the PN graft. Axons arising from the SCG elongated the whole length of the graft, crossed the graft-brain interface and extended into brain regions adjacent to the denervated striatum up to 2037 micrometer from the graft insertion site. This work shows that the ingrowth of catecholamine-regenerating axons from the SCG to dopamine-depleted brain parenchyma significantly reduces behavioral abnormalities in hemiparkinsonian rats. This effect cannot be ascribed either to the brain cavitation or to the PN tissue placement in the brain.
为了逆转中枢多巴胺系统破坏后出现的帕金森综合征，已将颈上神经节（SCG）移植到成年大鼠脑中。然而，这种方法的主要局限性在于，直接移植到脑内后，移植的SCG中会发生大量细胞死亡。在成年大鼠中，将6-羟基多巴胺（6-OHDA）立体定向注射到右侧黑质（SN）。一个月后，使用阿扑吗啡诱导的旋转试验评估多巴胺去神经支配情况。在试验呈阳性的大鼠中，将自体周围神经（PN）移植物从右侧颈部区域穿隧至同侧顶叶皮质。PN移植物的一端缝合到SCG横断的节后分支，另一端插入手术创建的皮质腔。在术后3天以及术后1、3和5个月再次进行阿扑吗啡试验。使用光镜和电镜以及酪氨酸羟化酶免疫组织化学和辣根过氧化物酶示踪方法对脑、SCG和PN移植物进行研究。移植后3天，与术前试验相比，阿扑吗啡试验无显著差异。相反，移植后1、3和5个月，旋转次数分别减少了69%（±20.2）、66.6%（±17.1）和72.5%（±11.3）。接受游离PN移植物植入脑并切断SCG节后分支的对照大鼠术后阿扑吗啡试验未显示显著变化。组织学检查显示，PN移植物大多由小口径无髓鞘轴突重新支配。通常投射到节后分支的SCG神经元群体中约40%在轴突切断后存活，并将横断的轴突再生到PN移植物中。源自SCG的轴突延伸至移植物全长，穿过移植物-脑界面，并延伸到去神经纹状体相邻的脑区，距离移植物插入部位达2037微米。这项研究表明，从SCG向多巴胺耗竭的脑实质生长的儿茶酚胺再生轴突显著减少了偏侧帕金森病大鼠的行为异常。这种效应既不能归因于脑空化，也不能归因于PN组织在脑内的放置。
