Increased glutamate in CSF and plasma of patients with HIV dementia

Increased glutamate in CSF and plasma of patients with HIV dementia
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DOI:
10.1212/wnl.57.4.671
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发表时间:
2001-08-28
期刊:
影响因子:
9.9
通讯作者:
Frattola, L
Frattola, L
中科院分区:
医学1区
文献类型:
--
作者:
Ferrarese, C;Aliprandi, A;Frattola, L

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背景:实验证据表明,兴奋性毒性可能在HIV诱导的神经退行性变中起主要作用。然而,很少有研究调查内源性谷氨酸在HIV痴呆患者中的作用。目的:分析30例不同痴呆程度的艾滋病患者的脑脊液和血浆谷氨酸水平,并与10例其他神经系统疾病患者、11例健康对照者和10例阿尔茨海默型痴呆患者进行比较。方法:采用反相高效液相色谱法和荧光分析法测定脑脊液和血浆谷氨酸水平。结果如下:与正常对照受试者相比,HIV患者CSF中的谷氨酸水平增加了5倍(p = 0.001),阿尔茨海默型痴呆患者(p < 0.0001)和其他神经系统疾病患者(p < 0.01)。脑脊液谷氨酸水平与痴呆程度(p < 0.02)和脑萎缩程度(p < 0.002)有关。HIV患者的血浆水平也较高(p < 0.0001),但与临床或影像学特征无关。结论:CSF谷氨酸升高可能起源于CNS,并可能在HIV痴呆中发挥致病作用,因此支持使用谷氨酸受体拮抗剂治疗这些患者。
Background: Experimental evidence suggests that excitotoxicity might play a major role in HIV-induced neurodegeneration. However, few studies have investigated the role of endogenous glutamate in patients with HIV dementia. Objective: To analyze CSF and plasma glutamate levels in 30 patients with AIDS with different dementia severity compared with 10 patients with other neurologic disorders, 11 healthy control subjects, and 10 patients with Alzheimer-type dementia. Methods: CSF and plasma glutamate levels were measured by reverse-phase high-performance liquid chromatography followed by fluorometric analysis. Results: Glutamate CSF levels were increased fivefold in the patients with HIV vs normal control subjects (p = 0.001), patients with Alzheimer-type dementia (p < 0.0001), and patients with other neurologic disorders (p < 0.01). CSF glutamate levels were also related to the degree of dementia (p < 0.02) and brain atrophy (p < 0.002). Plasma levels were also higher in the patients with HIV (p < 0.0001) but did not correlate with either clinical or imaging features. Conclusion: Increased CSF glutamate may originate within the CNS and may play a pathogenetic role in HIV dementia, thus supporting the treatment of these patients with glutamate receptor antagonists.