Advances in neurological injury and sequelae of cerebral malaria

doi:10.12140/j.issn.1000-7423.2026.02.022

Abstract

Abstract:

Cerebral malaria is one of the most fatal complications of Plasmodium falciparum infection, characterised clinically by altered consciousness or coma. Asexual P. falciparum parasites can be detected in peripheral blood, after exclusion of other causes of encephalopathy. The mortality rate of this disease can reach up to 20%, with approximately 15%-25% of survivors experiencing varying degrees of long-term neurological dysfunction, significantly impairing quality of life and social functioning. Current research has identified the retention of infected red blood cell in cerebral microvasculature, neuroinflammatory cascades, and blood-brain barrier disruption as core pathogenic mechanisms; however, the molecular regulatory networks underlying these processes remain incompletely elucidated. In this article, we systematically review recent research progress on the pathogenesis and neurological sequelae of cerebral malaria, focusing on key links in central nervous system damage, with the aim of providing a theoretical basis for the development of targeted adjuvant therapies and interventions.

Key words: Cerebral malaria, Neuroinflammation, Blood-brain barrier, Neurological sequelae, Post-malaria neurological syndrome

CLC Number:

R531.3

CUI Weiwei, CHENG Yang. Advances in neurological injury and sequelae of cerebral malaria[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2026, 44(2): 296-304.

Figures/Tables 3

References 96

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炎症因子	主要来源	靶细胞/作用部位	信号通路/分子机制	神经病理效应	文献
TNF-α	活化的巨噬细胞、T细胞	血管内皮细胞、星形胶质细胞	ICAM-1/VCAM-1上调，激活NF-κB通路，协同凝血酶增加屏障通透性	增加内皮通透性，诱导细胞凋亡，激活黏附分子表达	[21-22]
IFN-γ	CD8⁺ T细胞、自然杀伤细胞	小胶质细胞、脑实质细胞	JAK-STAT1、IFN/STAT1/IRF1	激活小胶质细胞，协同TNF-α增强炎症反应	[23-24]
IFN-β	脑内皮细胞	内皮细胞、免疫细胞	STING1/IFN-β/CXCL10轴	破坏血脑屏障，招募免疫细胞致脑实质炎症，神经元损伤	[25-26]
IL-1β	巨噬细胞、小胶质细胞	神经元、内皮细胞	NLRP3炎症小体、NF-κB	在实验性脑型疟模型中作用存争议（部分研究提示并非必需）	[27-28]
IL-6	巨噬细胞、胶质细胞、T细胞等	脑内皮细胞、神经元	gp130/STAT3、SOCS3	促进急性期反应，可能影响神经元存活及可塑性	[9,29]
CXCL10	内皮细胞、T细胞	CD8⁺ T细胞	CXCR3趋化轴	促进细胞毒性T淋巴细胞向脑组织募集，加剧血管周围炎性浸润	[30-31]
IL-10	调节性T细胞、B细胞	巨噬细胞、T细胞	STAT3	抑制促炎细胞因子产生，负调控炎症反应	[32-33]
miR-155	炎性细胞、内皮细胞	密封蛋白-1 mRNA	抑制TJP表达	破坏血脑屏障结构，促进血管源性脑水肿形成	[34-35]
内皮素-1	内皮细胞、血管平滑肌	脑微血管	内皮素-A/内皮素-B受体，MAPK/活性氧	收缩血管、诱导缺血，加重神经功能障碍	[36-37]
骨桥蛋白	巨噬细胞、星形胶质细胞	小胶质细胞、T细胞	整合素/CD44结合，NF-κB与MAPK通路	与炎症升高相关，可能成为提示晚期认知风险的潜在标志物	[38]

认知域	损伤时间进程	恢复/持续情况	代表性研究	文献
工作记忆	发病后3~6个月出现明显下降	部分随时间缓解，部分长期存在	脑型疟患者6个月后工作记忆缺陷约21%，显著高于对照	[55-56]
注意力	发病后3~6个月即受损	可持续至24个月或更久	脑型疟患儿注意缺陷检出率16.7%~17.0%，提示持续性认知影响	[57-58]
语言与命名能力	多于恢复期显现	恢复有限，部分长期存在	儿童病例中可见语言表达或理解迟缓，成人相对少见	[51]
行为能力	潜伏期6~12个月	多呈慢性过程	约10%脑型疟幼儿出现注意缺陷多动障碍或行为障碍	[59-60]
视觉空间能力	急性期即可受损	少见长期缺陷	多与皮质病变相关，MRI改变与早期干预有关	[61]
运动协调/小脑功能	急性或早期恢复期出现	部分可随康复训练改善	人群与动物研究均提示运动和协调能力损伤	[62-63]