Pipecolic Acid, a Putative Mediator of the Encephalopathy of Cerebral Malaria and the Experimental Model of Cerebral Malaria.
Pipecolic Acid, a Putative Mediator of the Encephalopathy of Cerebral Malaria and the Experimental Model of Cerebral Malaria.
复制标题
哌可酸，脑型疟疾脑病和脑型疟疾实验模型的假定介质。
DOI：
10.1093/infdis/jiab615
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Daily,JohannaP
中科院分区：
文献类型：
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作者：
Keswani,Tarun;Obeidallah,Aisha;Nieves,Edward;Sidoli,Simone;Fazzari,Melissa;Taylor,Terrie;Seydel,Karl;Daily,JohannaP
背景我们探讨了脑型疟疾昏迷的代谢病因。方法比较了马拉维脑型疟疾和轻度恶性疟原虫疟疾患儿的血浆代谢物。一个候选分子进一步研究疟疾动物模型中。结果临床异常浓度的哌啶酸（PA）存在于CM血浆中，在轻度疟疾样品中几乎正常。PA经肾脏清除，PA血液水平升高与肾功能不全相关，仅在CM受试者中存在。先前的研究表明，PA具有神经调节作用，并由疟疾寄生虫产生。在实验性脑型疟疾（ECM）模型中，伯氏疟原虫ANKA感染动物的PA脑水平与正常行为呈负相关，并与血脑屏障（BBB）通透性相关。感染疟疾物种，不诱导神经系统异常或表现血脑屏障通透性的小鼠有升高的血浆PA水平类似于ECM血浆在7天postinfection;然而，他们有低PA水平的大脑相比，ECM小鼠大脑在7天postinfection.ConclusionsOur模型表明，疟疾产生的PA诱导昏迷CM和ECM。血脑屏障通透性的作用和PA神经调节机制在CM中需要进一步的研究。
BackgroundWe explored a metabolic etiology of cerebral malaria (CM) coma.MethodsPlasma metabolites were compared between Malawian children with CM and mildPlasmodium falciparummalaria. A candidate molecule was further studied in animal models of malaria.ResultsClinically abnormal concentrations of pipecolic acid (PA) were present in CM plasma, and nearly normal in mild malaria samples. PA is renally cleared and the elevated PA blood levels were associated with renal insufficiency, which was present only in CM subjects. Prior studies demonstrate that PA has neuromodulatory effects and is generated by malaria parasites. PA brain levels inPlasmodium bergheiANKA–infected animals in the experimental cerebral malaria (ECM) model inversely correlated with normal behavior and correlated with blood-brain barrier (BBB) permeability. Mice infected with malaria species that do not induce neurological abnormalities or manifest BBB permeability had elevated plasma PA levels similar to ECM plasma at 7 days postinfection; however, they had low PA levels in the brain compared to ECM mice brains at 7 days postinfection.ConclusionsOur model suggests that malaria-generated PA induces coma in CM and in ECM. The role of BBB permeability and the mechanisms of PA neuromodulation in CM will require additional investigation.