Tulipan N, Luo S Q, Allen G S, Whetsell W O
Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Exp Neurol. 1988 Dec;102(3):325-32. doi: 10.1016/0014-4886(88)90227-0.
Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.
将新生纹状体组织移植到成年大鼠的纹状体中。当立即用纹状体内注射 kainic 酸或喹啉酸进行刺激时，可防止兴奋性毒性损伤。30 天后，这些相同的移植受体接受了另一次兴奋性毒素注射。纹状体内的移植组织继续减轻毒素诱导的损伤。据推测，移植的细胞不仅存活，而且它们可能继续产生某种或某些物质，这些物质可在至少 30 天内防止兴奋性毒素诱导的损伤。先前的研究表明，新生纹状体组织移植可保护受体纹状体免受 kainic 酸毒性的影响。在接下来的研究中表明，这种移植也能保护纹状体免受喹啉酸的影响，喹啉酸是一种内源性兴奋性毒素，可诱导类似 kainate 的神经元变性，并与亨廷顿舞蹈病的发病机制有关。据推测，纹状体移植的有益作用可能持续足够长的时间以减轻慢性毒性损伤。因此，这种移植可能代表了一种治疗亨廷顿舞蹈病和其他神经退行性疾病的方法，在这些疾病中，内源性或外源性毒素被认为是致病因素。
