脑型疟疾的神经血管病理生理学和新兴生物标志物:综合视角。

IF 3 Q2 CLINICAL NEUROLOGY
Damian Pikor, Mikołaj Hurła, Natalia Banaszek-Hurła, Alicja Drelichowska, Małgorzata Paul
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引用次数: 0

摘要

脑型疟疾是恶性疟原虫感染引起的一种危及生命的神经系统并发症,也是撒哈拉以南非洲流行区儿童死亡的主要原因。临床定义为昏迷伴外周寄生虫血症,无其他病因。从病理学上讲,寄生红细胞在脑微血管中的细胞粘附,以及广泛的炎症反应和内皮细胞激活,导致了严重的微血管损伤。这种损伤包括血脑屏障的破坏和多因素脑水肿(血管源性和细胞毒性)的发展,导致颅内压升高和弥漫性脑肿胀,在致命病例中可以在影像学上看到。最近在这些流行地区的儿童队列中进行的高分辨率MRI研究已经确定了特征性的神经影像学发现,如基底节区梗死、脑干病变和胼胝体异常,这些都有力地预测了不良预后。值得注意的是,寄生红细胞和活化内皮细胞释放的循环细胞外囊泡已成为微血管炎症的有效介质。细胞外囊泡含有寄生虫来源的抗原和宿主炎症信号,暗示它们与疾病机制有关。目前正在研究这些囊泡作为严重疟疾的新型诊断和预后生物标志物。重要的是,脑型疟疾的幸存者经常遭受持续的神经认知障碍、行为问题和癫痫,这强调了在急性期预防继发性神经元损伤以减少长期残疾的必要性。综上所述,这些见解突出了脑疟疾中脑微血管病理和神经预后之间的相互作用。这篇综述综合了脑疟疾的病理生理学和前沿诊断方法的最新进展。它强调了新的治疗靶点和神经保护策略,可能使精确医学方法旨在预防幸存者的持久神经残疾。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neurovascular Pathophysiology and Emerging Biomarkers in Cerebral Malaria: An Integrative Perspective.

Cerebral malaria is a life-threatening neurological complication of Plasmodium falciparum infection and a leading cause of pediatric mortality in endemic regions of sub-Saharan Africa. It is defined clinically by coma accompanied by peripheral parasitemia, without alternative causes. Pathogenetically, cytoadherence of parasitized erythrocytes in the cerebral microvasculature, together with a widespread inflammatory response and endothelial activation, causes profound microvascular injury. This injury includes disruption of the blood-brain barrier and the development of multifactorial cerebral oedema (both vasogenic and cytotoxic), resulting in elevated intracranial pressure and often diffuse brain swelling as seen on imaging in fatal cases. Recent high-resolution MRI studies in pediatric cohorts from these endemic regions have identified characteristic neuroimaging findings such as basal ganglia infarcts, brainstem lesions, and corpus callosum abnormalities that strongly predict poor outcomes. Notably, circulating extracellular vesicles-released by parasitized erythrocytes and activated endothelial cells have emerged as potent mediators of microvascular inflammation. Extracellular vesicles contain parasite-derived antigens and host inflammatory signals, implicating them in disease mechanisms. These vesicles are under investigation as novel diagnostic and prognostic biomarkers for severe malaria. Importantly, survivors of cerebral malaria often endure persistent neurocognitive impairments, behavioral problems, and epilepsy, underscoring the need to prevent secondary neuronal injury during the acute phase to reduce long-term disability. Taken together, these insights highlight the interplay between cerebral microvascular pathology and neurological outcome in cerebral malaria. This review synthesizes recent advances in the pathophysiology of cerebral malaria and cutting-edge diagnostic modalities. It highlights novel therapeutic targets and neuroprotective strategies that may enable precision medicine approaches aimed at preventing lasting neurological disability in survivors.

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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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