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NEUROPROTECTOR ROLE OF PIOGLITAZONE ON EXPERIMENTAL MODEL OF CEREBRAL MALARIA IMPROVES SURVIVAL AND REDUCES CEREBRAL LEUKOCYTE RECRUITMENT
Author(s) -
LimborçoFilho Marcelo,
OliveiraLima Onésia Cristina,
Kangussu Lucas Miranda,
Marins Fernanda Ribeiro,
Oliveira Antônio Carlos,
CarvalhoTavares Juliana
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb495
Subject(s) - cerebral malaria , pioglitazone , parenchyma , medicine , proinflammatory cytokine , neuroprotection , pathogenesis , pharmacology , inflammation , pathology , malaria , endocrinology , diabetes mellitus , plasmodium falciparum , type 2 diabetes
Pioglitazone(PIO) acts as an anti‐inflammatory drug, and therefore, we sought to investigate its role on experimental cerebral malaria(CM). PIO treated C57BL/6 mice(TM) showed protection against infection compared to non‐treated mice, as evidenced by delay in mortality and clinical improvement without altering the parasitemia. TM showed a decrease in rolling(1,6±0,5 vs 4,9±0,8 cels/min) and adhesion(3,4±0,8 vs 11,1±1,6 cels/100um) leukocytary process on pia mater endothelium(5dpi), as well a reduction on cerebral myeloperoxidase activity(1,1±0,2 vs 2,5±0,44; 1,95±0,25 vs 3,4±0,4 UR/brain 100mg; 5–6 dpi, respectively). By histopathological analysis, TM show a reduction on vascular obstruction and bleeding on brain parenchyma(6 dpi). This partial neuroprotection(5–6 dpi) was confirmed with reduction on Evan's blue dye leakage into the brain parenchyma of TM(8,32±2,08 vs 13,82±1,14; 10,61±1,29 vs 16,13±1,07 dye ug/brain 100mg), as well a reduction of brain hemorrhage(21,3±1,8 vs 31,8±1,7;26,7±2,8 vs 37,7±3,9 Hb ug/brain 100mg). This therapeutic strategy suggests that PIO is relevant to delay CM pathogenesis probably due its property of inhibiting gen transcription of proinflammatory mediators. CAPES/CNPq