Cerebrospinal fluid studies in children with cerebral malaria: An excitotoxic mechanism?
Cerebrospinal fluid studies in children with cerebral malaria: An excitotoxic mechanism?
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DOI：
10.4269/ajtmh.2000.62.284
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发表时间：
2000-02-01
影响因子：
3.3
通讯作者：
Surtees, R
中科院分区：
文献类型：
--
作者：
Dobbie, M;Crawley, J;Surtees, R
脑型疟疾的发病机制还知之甚少。一种假说认为，脑内小胶质细胞和星形胶质细胞的激活可能通过兴奋性毒性机制引起大脑症状。对97名患有脑型疟疾的肯尼亚儿童进行了脑脊液采样，85%的儿童在入院48小时内进行了脑脊液采样。与年龄匹配的参考范围相比，兴奋毒素喹啉酸(几何平均比率脑型疟疾/参考人口[95%可信限]=14.1[9.8-20.4]，P<；0.001)和总新喋呤(10.9[9.113.0]，P<；0.001)浓度有较大的增加，四氢生物蝶呤、二氢生物蝶呤和5-羟基吲哚乙酸的浓度增幅较小。色氨酸浓度没有变化。相反，硝酸盐和亚硝酸盐浓度降低(几何平均比率=0.45P<；0.001)。在严重程度逐渐增加的结果组中，喹啉酸浓度有逐渐增加的趋势。喹啉酸浓度升高提示兴奋性毒性机制可能参与了脑型疟疾的发病机制。
The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an age-matched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations were decreased (geometric mean ratio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.