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Title: Nuclear factor kappa B modulates apoptosis in the brain endothelial cells and intravascular leukocytes of fatal cerebral malaria
Authors: Chuchard Punsawad
Yaowapa Maneerat
Urai Chaisri
Kwannan Nantavisai
Parnpen Viriyavejakul
Mahidol University. Faculty of Tropical Medicine. Department of Tropical Pathology
Keywords: Malaria;Cerebral malaria;Nuclear factor kappa B;NF-κB p65;Cleaved caspase-3;Apoptosis;Immunohistochemistry;Open Access article
Issue Date: 2013
Citation: Malaria Journal. Vol.12, (2013), 260
Abstract: Background: Cerebral malaria (CM) caused by Plasmodium falciparum is known to be associated with the sequestration of parasitized red blood cells (PRBCs) in the microvasculature and the release of soluble cytokines. In addition, the involvement of signaling molecules has gained wide interest in the pathogenesis of CM. An important signaling factor, nuclear factor kappa B (NF-κB) is known to regulate apoptosis. This work aimed to study the expression of NF-κB p65 and its correlation with apoptosis in the brain of fatal CM. Methods: The expression of NF-κB p65 and cleaved caspase-3 in the brain of fatal P. falciparum malaria cases was investigated by immunohistochemistry. Histopathological features were analysed together with the correlations of NF-κB p65 and cleaved caspase-3 expression. Results: NF-κB p65 activation and cleaved caspase-3 expression were significantly increased in the neurons, glial cells, vascular endothelial cells (ECs) and intravascular leukocytes of the brain in fatal CM, compared with the control brain (p < 0.001) and non-cerebral malaria (NCM) (p = 0.034). The percentage of neurons that expressed nuclear NF-κB p65 showed a positive correlation with the total score of histopathological changes (rs = 0.678; p = 0.045). Significant positive correlations were established between vascular ECs NF-κB index and ECs apoptotic index (rs = 0.717; p = 0.030) and between intravascular leukocytes NF-κB index and leukocytes apoptotic index (rs = 0.696; p = 0.037) in fatal CM. Conclusions: This study documented that NF-κB p65 is one of the signaling factors that modulates apoptosis in the brain ECs and intravascular leukocytes of fatal CM.
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