Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria
Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria
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DOI：
10.1186/s12936-017-1954-1
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发表时间：
2017-07-28
期刊：
影响因子：
3
通讯作者：
John, Chandy C.
中科院分区：
文献类型：
--
作者：
Holmberg, Dag;Franzen-Rohl, Elisabeth;John, Chandy C.
背景：四分之一的脑型疟疾（CM）患儿在急性病后2年内仍有认知后遗症。脑的犬尿氨酸途径形成神经活性代谢物，例如NMDA受体拮抗剂犬尿烯酸（KYNA），与其他CNS感染的长期认知功能障碍有关。在本研究中，犬尿氨酸途径和神经/认知并发症的儿童CM.Methods：脑脊髓液（CSF）浓度KYNA及其前体犬尿氨酸在69乌干达儿童承认CM穆拉戈医院，坎帕拉，乌干达，2008年至2013年之间进行了评估。将CSF犬尿氨酸和KYNA与CSF细胞因子水平、急性和长期神经系统并发症以及长期认知障碍进行比较。CSF犬尿氨酸和KYNA从8个瑞典儿童没有神经系统或感染性疾病入院Astrid Lindgren的儿童医院进行了量化和用于comparation.Results：CM的儿童有显着较高的CSF浓度犬尿氨酸和KYNA比瑞典儿童（P < 0.0001），和CSF犬尿氨酸和KYNA呈正相关。在CM儿童中，CSF犬尿氨酸和KYNA浓度与所有年龄儿童的昏迷时间相关（分别为P = 0.003和0.04），CSF犬尿氨酸浓度与整体认知能力较差相关（P = 0.056）注意力（P = 0.003）在>= 5岁的儿童中进行12个月随访。CSF KYNA和犬尿氨酸在患有CM的儿童中升高，表明对多巴胺能和胆碱能信号传导的抑制。这种抑制可能会导致急性长期昏迷和长期的注意力和认知障碍。
Background: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated.Methods: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison.Results: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children >= 5 years old.Conclusions: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.