NEUROPROTECTOR ROLE OF PIOGLITAZONE ON EXPERIMENTAL MODEL OF CEREBRAL MALARIA IMPROVES SURVIVAL AND REDUCES CEREBRAL LEUKOCYTE RECRUITMENT

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