Björklund H, Olson L, Dahl D, Schwarcz R
Brain Res. 1986 Apr 23;371(2):267-77. doi: 10.1016/0006-8993(86)90362-8.
Astroglial reactions to intrastriatal and intrahypothalamic injections of the endogenous excitotoxin quinolinic acid (50 micrograms in 1 microliter) were studied in adult rats, using immunohistochemistry with antiserum to glial fibrillary acidic protein. Animals were sacrificed 6 h, 24 h, 3, 7 and 30 days or 1 year after the injection. Six and 24 h after quinolinic acid, the amount of glial fibrillary acidic protein-like immunoreactivity in the injected striatum was lower than in controls but returned to a normal level at 3 days. Not until 7 days was a clear striatal gliosis apparent, as evidenced by an increased density of glial fibrillary acidic protein-positive structures and brightly fluorescent, clearly hypertrophic cells. This gliosis was even more developed in animals sacrificed 30 days postoperatively. A weak astrocytic reaction was also observed in the ipsilateral corpus callosum at 6 h after quinolinic acid. By 3 days, a marked gliosis restricted to the injected hemisphere was present throughout corpus callosum and cortex cerebri. In animals sacrificed 30 days after quinolinic acid the extrastriatal astrocytic reaction was clearly diminished, although the striatal gliosis was still prominent. One year postinjection, no obvious gliosis could be observed in cortex cerebri or corpus callosum while striatal tissue, now markedly reduced in volume, was clearly gliotic. Using neurofilament antiserum, increased fluorescence intensity was noted in striatal nerve bundles during the first day after an intrastriatal quinolinic acid injection and persisted 1 year postoperatively. Controls were similarly injected with an equimolar amount of nicotinic acid, the non-excitatory, non-neurotoxic decarboxylation product of quinolinic acid. No changes in immunoreactivity of glial fibrillary acidic protein or neurofilament were found in these animals. In animals treated intrahypothalamically, a spherical central area almost devoid of glial fibrillary acidic protein-immunoreactivity was noted around the injection site 7 days after quinolinic acid administration. Around this area, gliosis was observed. Apart from a very restricted gliotic reaction around the needle tract, no astrocytic reaction was observed in nicotinic acid-injected control animals. We conclude that quinolinic acid causes both reversible and long-lasting gliosis when injected into the rat striatum. As a natural brain metabolite, quinolinic acid may constitute a particularly valuable tool for the elucidation of a possible role of glia in neurodegenerative disorders.
利用抗胶质纤维酸性蛋白抗血清进行免疫组织化学，研究成年大鼠纹状体内和下丘脑内注射内源性兴奋性毒素喹啉酸（1微升含50微克）后星形胶质细胞的反应。在注射后6小时、24小时、3天、7天、30天或1年处死动物。注射喹啉酸后6小时和24小时，注射侧纹状体内胶质纤维酸性蛋白样免疫反应性的量低于对照组，但在3天时恢复到正常水平。直到7天时，明显的纹状体胶质增生才显现出来，表现为胶质纤维酸性蛋白阳性结构的密度增加以及明亮荧光、明显肥大的细胞。在术后30天处死的动物中，这种胶质增生更为明显。在注射喹啉酸后6小时，在同侧胼胝体中也观察到轻微的星形胶质细胞反应。到3天时，整个胼胝体和大脑皮层中均出现明显的胶质增生，且仅限于注射侧半球。在注射喹啉酸后30天处死的动物中，纹状体以外的星形胶质细胞反应明显减弱，尽管纹状体胶质增生仍然显著。注射1年后，在大脑皮层或胼胝体中未观察到明显的胶质增生，而此时纹状体组织体积明显减小，且明显发生了胶质化。使用神经丝抗血清，在纹状体内注射喹啉酸后的第一天，纹状体神经束中的荧光强度增加，并在术后1年持续存在。对照组同样注射等摩尔量的烟酸，即喹啉酸的非兴奋性、非神经毒性脱羧产物。在这些动物中未发现胶质纤维酸性蛋白或神经丝免疫反应性的变化。在进行下丘脑内注射的动物中，在注射喹啉酸7天后，注射部位周围出现一个几乎没有胶质纤维酸性蛋白免疫反应性的球形中心区域。在该区域周围观察到胶质增生。除了针道周围非常局限的胶质化反应外，在注射烟酸对照组动物中未观察到星形胶质细胞反应。我们得出结论，喹啉酸注入大鼠纹状体时会引起可逆和持久的胶质增生。作为一种天然的脑代谢产物，喹啉酸可能是阐明胶质细胞在神经退行性疾病中可能作用的一种特别有价值的工具。
