Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam
Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam
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DOI：
10.1212/wnl.55.1.104
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发表时间：
2000-07-12
期刊：
影响因子：
9.9
通讯作者：
Turner, GDH
中科院分区：
文献类型：
--
作者：
Brown, HC;Chau, TTH;Turner, GDH
背景：红细胞内寄生虫恶性疟原虫在脑血管内诱发危及生命的脑型疟疾（CM）神经综合征，而不进入脑实质。
目的：1）评估脑脊液（CSF）作为脑型疟疾期间大脑中发生的特定病理过程指标的用途；2）将其与其他神经系统疾病和感染性疾病进行比较，以了解脑型疟疾独特的致病特征；3）检验脑型疟疾涉及血脑屏障（BBB）特定功能破坏这一假设。
方法：1）采用放射免疫扩散测定法检测匹配的血浆和脑脊液样本中的白蛋白和IgG，作为血脑屏障完整性和鞘内IgG产生的指标；2）采用酶联免疫吸附测定（ELISA）检测可溶性细胞内黏附分子 - 1和sE - 选择素、细胞因子肿瘤坏死因子 - α和转化生长因子 - β1以及基质金属蛋白酶MMP - 9，以检测大脑内的细胞活化和炎症反应。
结果：在少数脑型疟疾病例中，白蛋白和IgG指数仅表明血脑屏障有极轻微的破坏程度，大多数仍在正常范围内。相比之下，隐球菌性、结核性和急性细菌性脑膜炎导致脑脊液成分发生可检测到的变化以及血脑屏障破坏的证据。
结论：与其他神经系统感染相比，脑型疟疾似乎仅涉及血脑屏障完整性的细微功能变化，实质内炎症反应极小。这使得人们关注脑型疟疾中脑微血管内及其周围的局部事件，而非表明广泛的实质疾病。
Background: The intraerythrocytic parasite Plasmodium falciparum induces the life-threatening neurologic syndrome of cerebral malaria (CM) from within cerebral blood vessels, without entering the brain parenchyma. Objectives: 1) To assess the use of CSF as an indicator of specific pathologic processes occurring in the brain during CM; 2) to compare this with other neurologic and infectious diseases to understand the distinct pathogenic features of CM; 3) to test the hypothesis that CM involves a specific functional breakdown of the blood-brain barrier (BBB). Methods: 1) Radial immunodiffusion assays to detect albumin and IgG in matched plasma and CSF samples as indicators of BBB integrity and intrathecal IgG production; and 2) ELISA for soluble intracellular adhesion molecule-1 and sE-selectin, the cytokines tumor necrosis factor-alpha and transforming growth factor-beta 1, and the matrix metalloproteinase MMP-9, to detect cellular activation and inflammatory responses within the brain. Results: Albumin and IgG indices implied only minimal degree of BBB breakdown in a few cases of CM, with most remaining within the normal range. In contrast, cryptococcal, tubercular, and acute bacterial meningitis produced detectable changes in the composition of the CSF and evidence of BBB breakdown. Conclusions: CM appears to involve only subtle functional changes in BBB integrity with minimal intraparenchymal inflammatory responses compared with other neurologic infections. This focuses attention on local events within and around the cerebral microvasculature in CM, rather than indicating widespread parenchymal disease.