title: Nuclear factor kappa B modulates apoptosis in the brain endothelial cells and intravascular leukocytes of fatal cerebral malaria.
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.
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, Thailand.
authors.forename: Chuchard
authors.initials: C
authors.lastname: Punsawad
authors.forename: Yaowapa
authors.initials: Y
authors.lastname: Maneerat
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
authors.forename: Kwannan
authors.initials: K
authors.lastname: Nantavisai
authors.forename: Parnpen
authors.initials: P
authors.lastname: Viriyavejakul
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001921:Brain / Q000276:immunology / Q000473:pathology*; D053148:Caspase 3 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000502:physiology*; D016779:Malaria, Cerebral / Q000473:pathology*; D016778:Malaria, Falciparum / Q000150:complications* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D053148:Caspase 3
references.citation: Neuropathol Appl Neurobiol. 1999 Aug;25(4):331-40
references.pmid: 10476050
references.citation: Am J Pathol. 1999 Aug;155(2):395-410
references.pmid: 10433933
references.citation: Infect Immun. 2005 Mar;73(3):1764-70
references.pmid: 15731077
references.citation: Brain Res. 2000 Dec 1;885(1):111-6
references.pmid: 11121536
references.citation: Apoptosis. 2007 Apr;12(4):695-705
references.pmid: 17143787
references.citation: Am J Pathol. 1997 Apr;150(4):1473-86
references.pmid: 9095002
references.citation: Science. 1995 Mar 10;267(5203):1456-62
references.pmid: 7878464
references.citation: Eur Cytokine Netw. 2002 Apr-Jun;13(2):173-85
references.pmid: 12101073
references.citation: Thromb Haemost. 2005 Aug;94(2):336-40
references.pmid: 16113823
references.citation: Parasitology. 1994;108 Suppl:S19-28
references.pmid: 8084651
references.citation: Cytokine Growth Factor Rev. 1999 Mar;10(1):27-39
references.pmid: 10379910
references.citation: Cancer Res. 1997 Apr 15;57(8):1605-13
references.pmid: 9108467
references.citation: Int J Parasitol. 2006 Apr;36(4):485-96
references.pmid: 16500656
references.citation: J Immunol. 2006 Jan 15;176(2):1180-4
references.pmid: 16394007
references.citation: Am J Pathol. 1994 Nov;145(5):1057-69
references.pmid: 7526692
references.citation: Glia. 1996 Jan;16(1):51-64
references.pmid: 8787773
references.citation: Glia. 1997 Feb;19(2):91-103
references.pmid: 9034826
references.citation: Infect Immun. 2006 Jun;74(6):3262-70
references.pmid: 16714553
references.citation: J Immunol. 1996 Mar 1;156(5):1886-96
references.pmid: 8596041
references.citation: Neuropathol Appl Neurobiol. 2007 Oct;33(5):560-71
references.pmid: 17442059
references.citation: Parasitol Today. 1994 Oct;10(10):410-2
references.pmid: 15275552
references.citation: J Infect Dis. 2003 Apr 15;187(8):1283-90
references.pmid: 12696008
references.citation: J Pathol. 2004 Mar;202(3):265-73
references.pmid: 14991891
references.citation: Malar J. 2012 Jun 10;11:191
references.pmid: 22682094
references.citation: Cell. 2002 Apr;109 Suppl:S81-96
references.pmid: 11983155
references.citation: Blood. 2009 Nov 5;114(19):4243-52
references.pmid: 19713460
references.citation: Am J Pathol. 2002 Feb;160(2):655-66
references.pmid: 11839586
references.citation: Parasit Vectors. 2010 Nov 17;3:106
references.pmid: 21083888
references.citation: Redox Rep. 2001;6(3):137-42
references.pmid: 11523587
references.citation: Clin Neuropathol. 1993 May-Jun;12(3):142-6
references.pmid: 8100753