Heyes M P, Brew B J, Martin A, Price R W, Salazar A M, Sidtis J J, Yergey J A, Mouradian M M, Sadler A E, Keilp J
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Ann Neurol. 1991 Feb;29(2):202-9. doi: 10.1002/ana.410290215.
Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.
喹啉酸是一种“兴奋性毒性”代谢产物，也是N-甲基-D-天冬氨酸受体的激动剂。在感染1型人类免疫缺陷病毒（HIV-1）且神经功能正常或仅表现出获得性免疫缺陷综合征（AIDS）痴呆综合征不明确和亚临床症状的患者中，处于疾病早期（沃尔特·里德分期1和2期）的患者脑脊液（CSF）中喹啉酸浓度增加了两倍，而晚期患者（沃尔特·里德分期4至6期）平均高于正常水平3.8倍。然而，在患有临床明显的AIDS痴呆综合征、无菌性脑膜炎、机会性感染或肿瘤的患者中，CSF水平升高超过20倍，且通常与认知和运动功能障碍的严重程度平行。CSF中喹啉酸浓度与神经心理缺陷的严重程度显著相关。在用齐多夫定治疗AIDS痴呆综合征并用特定抗菌疗法治疗机会性感染后，CSF中喹啉酸水平随临床神经功能改善而下降。通过分析CSF与血清中喹啉酸水平之间的关系以及通过CSF:血清白蛋白比值测量的血脑屏障完整性，似乎CSF中喹啉酸水平可能主要源自脑内，也可能源自血清。虽然喹啉酸可能是大脑中宿主和病毒介导事件的另一个“标志物”，但喹啉酸已确定的兴奋性毒性作用以及该酸CSF水平升高的幅度增加了喹啉酸在与HIV-1感染相关的脑功能障碍发病机制中起直接作用的可能性。
