Assuntos
Síndrome Antifosfolipídica/diagnóstico , Isquemia Encefálica/diagnóstico , Hanseníase/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Humanos , Hanseníase/complicações , Hanseníase/imunologia , Hanseníase/patologia , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologiaRESUMO
Dapsone (4,4'-diaminodiphenylsulfone) is employed in the chemotherapy against leprosy. Dapsone also prevents neuronal damage induced by glutamate agonists. As glutamate excitotoxicity is implicated in the damage after ischemia, we tested the ability of dapsone to prevent ischemic injury in a model of permanent middle cerebral artery (MCA) occlusion in rats. Either dapsone (9.375 or 12.5 mg/kg doses) or vehicle were i.p. administered 30 min after occlusion. Rats from the control group showed a permanent neurological deficit after occlusion, while dapsone-treated groups improved significantly. Dapsone-treated animals showed a reduction of 93% (9.375 mg/kg dose) and 92% (12.5 mg/kg dose) in the infarction volume as compared to control values.
Assuntos
Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/prevenção & controle , Isquemia Encefálica/tratamento farmacológico , Dapsona/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Animais , Infarto Encefálico/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Hansenostáticos/farmacologia , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Resultado do TratamentoRESUMO
Rifampicin is an antibacterial agent that is widely used in tuberculosis and leprosy therapy. Interestingly, some experimental studies indicate that rifampicin acts as a hydroxyl radical scavenger and a glucocorticoid receptor activator. In this study, the neuroprotective effect of rifampicin was evaluated after transient and permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent or transient thread occlusion of the middle cerebral artery (MCA). Reperfusion in transient ischemia was initiated 30 min later by thread retraction. Rifampicin or vehicle were applied intraperitoneally before permanent or immediately after 30 min of transient ischemia. Later, 24 h after permanent or transient ischemia, animals were re-anesthetized and decapitated. Brain injury was evaluated by triphenyltetrazolium chloride staining (TTC), terminal transferase biotinylated-dUTP nick end labeling (TUNEL) and cresyl violet staining. A 20-mg/kg sample of rifampicin showed a significant neuroprotection after cerebral ischemia. The number of TUNEL-positive cells in the striatum, where disseminated tissue injury was observed, was also reduced by application of rifampicin as compared with vehicle-treated animals. The present report shows that administration of rifampicin efficiently reduces brain injury after permanent and transient focal cerebral ischemia in mice.