Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria

被引:49
作者
Medana, IM
Mai, NTH
Day, NPJ
Hien, TT
Bethell, D
Phu, NH
Farrar, J
White, NJ
Turner, GDH
机构
[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Malaria Res Grp, Oxford OX3 9DU, England
[2] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England
[3] Cho Quan Hosp, Wellcome Trust Res Unit, Ho Chi Minh City, Vietnam
[4] Cho Quan Hosp, Ctr Trop Dis, Ho Chi Minh City, Vietnam
关键词
heat shock; poly(ADP) ribose polymerase; caspase-3; apoptosis;
D O I
10.1046/j.0305-1846.2001.00360.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Immunohistochemical techniques have been used to investigate specific patterns of potentially reversible cellular injury, DNA damage, and apoptosis in the brainstems of Vietnamese patients who died of severe Plasmodium falciparum malaria. The degree and pattern of neuronal and glial stress responses were compared between patients with cerebral and non-cerebral malaria (CM), and appropriate non-malaria infected controls. The following markers were examined: (i) heat shock protein 70 (HSP70), for reversible injury; (ii) heme oxygenase-1. for oxidative stress: (iii & iv) two DNA-repair proteins. poly(ADP) ribose polymerase (PARP) and DNA-dependent protein kinase catalytic subunit: (v) poly(ADP) ribose. an end-product of PARP activity: and (vi) caspase-3-active, for apoptosis. Stress responses were found in a range of cell types as reflected by the widespread expression of HSP70. Oxidative stress predominated in the vicinity of vessels and haemorrhages. Some degree of DNA damage was found in the majority of malaria patients, but the distribution and frequency or the damage was much less than that observed in controls with irreversible neuronal injury. Similarly, caspase-3-active expression, its a measure of apoptosis, was no higher in the majority of malaria patients than the negative control cases, although 40% of CM cases expressed caspase-3-active in a small number of neurones of the pontine nuclei or within swollen axons of the pontocerebellar and corticospinal tracts. In conclusion, cells within the brainstem of all patients who died from severe malaria showed staining patterns indicative of considerable stress response and reversible neuronal injury. There was no evidence for a specific pattern of widespread irreversible cell damage in those patients with cerebral malaria.
引用
收藏
页码:421 / 433
页数:13
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