Roberts R C, DiFiglia M
Department of Neurology, Massachusetts General Hospital, Boston.
Synapse. 1989;3(4):363-71. doi: 10.1002/syn.890030410.
Large striatal neurons are spared in caudate tissue from postmortem brain of patients with Huntington's disease (HD) and in the rat caudate lesioned with excitotoxins at short postlesion intervals. In order to determine the survival of large neurons and other effects of excitotoxicity at longer postlesion intervals the rat caudate nucleus was examined 2, 7, and 30 weeks after intrastriatal injections of the excitotoxin, quinolinic acid. The caudate nucleus diminished in size progressively up to 30 weeks postlesion due to 1) shrinkage and compacting of the lesion zone and 2) reduction in area of intact caudate, apparently due to gradual loss of the remaining caudate neurons. In Nissl-stained sections of the lesion zone where total neuronal density was less than 5% of contralateral control, large neurons were present at all postlesion intervals, forming 38-58% of the remaining neurons. Unexpectedly, a fivefold reduction in the number of large neurons was observed between 2 and 30 weeks postlesion. Also, at 7 and 30 weeks postlesion most of the large neurons were confined to the peripheral region of the lesion. At all postlesion intervals, large neurons retained ultrastructural integrity and some synaptic inputs despite the severe disruption of the surrounding neuropil. Surrounding the lesion zone was a transition zone which exhibited a decrease in total neuronal density to 53-74% of control. In this region the density of large neurons was not diminished, and the proportion of large neurons was elevated in comparison to that of controls at all postlesion intervals. Findings suggest that following excitotoxic lesion of the caudate nucleus there are marked differences between short- and long-term postlesion intervals in the survival and distribution of large neurons. We speculate that an imbalance in the synaptic connections with other caudate neurons leads to the persistent loss of large neurons in the lesion zone at long postlesion intervals. A transition zone surrounding the lesion, where cell loss is less severe than in the lesion zone, exhibits features more characteristic of the neuropathology of HD.
在亨廷顿舞蹈病（HD）患者的尸检脑尾状核组织中，以及在损伤后短时间间隔内用兴奋性毒素损伤的大鼠尾状核中，大型纹状体神经元得以保留。为了确定更长损伤后间隔时间内大型神经元的存活情况以及兴奋性毒性的其他影响，在向纹状体内注射兴奋性毒素喹啉酸后2周、7周和30周对大鼠尾状核进行了检查。尾状核大小在损伤后30周内逐渐减小，原因如下：1）损伤区域的收缩和致密化；2）完整尾状核面积的减小，这显然是由于剩余尾状核神经元的逐渐丧失。在损伤区域的尼氏染色切片中，总神经元密度小于对侧对照的5%，在所有损伤后间隔时间均存在大型神经元，占剩余神经元的38% - 58%。出乎意料的是，在损伤后2周和30周之间观察到大型神经元数量减少了五倍。此外，在损伤后7周和30周，大多数大型神经元局限于损伤区域的周边。在所有损伤后间隔时间，尽管周围神经纤维严重受损，但大型神经元仍保持超微结构完整性和一些突触输入。围绕损伤区域的是一个过渡区，其总神经元密度降至对照的53% - 74%。在该区域，大型神经元的密度没有降低，并且在所有损伤后间隔时间，大型神经元的比例相对于对照有所升高。研究结果表明，尾状核兴奋性毒性损伤后，损伤后短期和长期间隔在大型神经元的存活和分布方面存在显著差异。我们推测，与其他尾状核神经元的突触连接失衡导致损伤后长期间隔时损伤区域大型神经元持续丧失。围绕损伤的过渡区，其细胞丢失比损伤区域轻，表现出更具HD神经病理学特征的特点。
