Nuffield Department of Clinical Laboratory Sciences, The John Radcliffe Hospital, University of Oxford, Oxford, UK.
Malar J. 2011 Sep 17;10:267. doi: 10.1186/1475-2875-10-267.
The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria.
The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF) receptor 2 and expression of the aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection.
The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02).
Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with fatal falciparum malaria. Enhanced expression of AQP4 water channels in the brainstem may, therefore, reflect a mix of both neuropathological or attempted neuroprotective responses to oedema formation.
脑水肿在恶性疟原虫性脑型疟疾的病理生理学中的作用存在争议。与严重恶性疟原虫疟疾相关的昏迷是多因素的，但与寄生红细胞的组织学证据相关，寄生虫在脑内血管中被隔离，导致小血管充血。为了确定这些变化是否导致血脑屏障的破坏，并导致血管周围或实质脑水肿，使用组织学、免疫组织化学和图像分析来定义成人致命性恶性疟原虫疟疾中水肿的组织学模式以及参与水平衡的特定分子途径的表达的普遍性。
检查了 20 名死于严重疟疾的成年越南患者的大脑，以寻找血管完整性受损的证据。对脑干切片进行免疫组织化学和图像分析，以检测血管内皮生长因子 (VEGF) 受体 2 的激活和水通道蛋白 aquaporin 4 (AQP4) 的表达。纤维蛋白原免疫染色被评估为血脑屏障渗漏和血管周围水肿形成的证据。与严重疟疾感染的临床、生化和神经病理学参数进行相关性分析。
在致命性恶性疟原虫感染中，水肿、血浆蛋白渗漏和 VEGF 信号的存在具有异质性，与生前昏迷无关。在大脑区域之间观察到血管完整性的差异，与大脑皮层或中脑相比，脑干的破坏最为普遍。在出现昏迷的病例中，脑干中 AQP4 染色的趋势更高，但统计学上无显著意义（P=0.02）。
在致命性恶性疟原虫疟疾的成年患者中，没有组织学上的脑水肿证据或免疫组织化学上的局部血管完整性丧失的证据与生前昏迷的发生相关。AQP4 水通道在脑干中的表达增强可能反映了脑水肿形成的神经病理学或试图神经保护的混合反应。
