Fisetina, um flavonóide que protege camundongos do dano neuronal e déficit de memória induzido por isquemia cerebral focal permanente

O acidente vascular cerebral (AVC) é uma doença comum e uma das maiores causas de morte eincapacidade em todo o mundo. O acidente vascular cerebral isquêmico focal (AVCi) o corredevido a uma redução do aporte sanguíneo para uma região cerebral, levando ao decréscimo de oxigênio e glicose nos tecidos, induzindo a uma cascata de eventos, incluindo o estresse oxidativo e inflamação, que culminam com a morte neuronal e, com isso uma perda rápida da função neurológica. A Fisetina é um membro do subgrupo flavonol pertencente aos flavonoides,encontrado em diversas frutas e vegetais que apresentam propriedades antiinflamatórias e antioxidantes. O objetivo deste trabalho foi estudar os efeitos da Fisetina sobre o dano neuronal e memória, resposta inflamatória e sinaptogênese em camundongos submetidos ao modelo experimental de isquemia cerebral focal permanente (pMCAO). Os foram animais divididosentre os grupos falso-operados, tratados com veículo ou fisetina (FIS) na dose de 50 mg/kg,isquemiados tratados com veículo e isquemiados tratados com FIS nas doses de 10, 30, e 50mg/kg via oral, 3 horas depois da eletrocauterização da artéria cerebral média. O modelo deisquemia cerebral focal permanente foi comprovado através do aumento significativo da área de infarto e dos déficits sensório-motores nos animais isquemiados, observado através da coloração com TTC e da avaliação neurológica...

Stroke is a common disease and a major cause of death and disability worldwide. The focalischemic stroke (ischemic stroke) occurs due to a reduced blood supply to brain region,leading to the decrease of oxygen and glucose in tissues, inducing a cascade of eventsincluding oxidative stress and inflammation, culminating with neuronal death and thus a rapidloss of neurological function. Fisetin is a member of subgroup belonging to the flavonolflavonoid found in many fruits and vegetables that have anti-inflammatory and antioxidantproperties. The objective of this work was to study the effects of fisetin on neuronal damageand memory, inflammatory response and synaptogenesis in mice undergoing experimentalmodel of permanent focal cerebral ischemia (pMCAO). Were animals divided between thefalse-operated groups treated with vehicle or fisetin (SIF) at a dose of 50 mg / kg-ischemictreated with vehicle and-ischemic treated with FIS in doses of 10, 30, and 50 mg / kg po 3hours after the middle cerebral artery electrocautery. The permanent focal cerebral ischemiamodel was proven by the significant increase in infarct area and sensorimotor deficits inischemicanimals, observed by staining with TTC and neurological evaluation...

The Effect of Moderate Hypothermia on Infarct Size and Early Change of Regional Cerebral Glucose Uptake in Permanent Focal Cerebral Ischemia in the Rat

Using a rat model, this study examined the cerebral protective effect of moderate hypothermia and evaluated the effect on early local metabolic change of permanent focal cerebral ischemia. The middle cerebral artery(MCA) of the rat was approached subtemporally and was occluded, and its surface was cooled. Cerebral infarct size was measured at 1, 4 and 7 days after MCA occlusion in non-treated(n=27), 2-hour hypothermia(n=27) and 3-hour hypothermia(n=27) group, respectively, and regional cerebral glucose uptake(rCGU) was determined at 1 and 4 hour after MCA occlusion in the non-treated(n=8) and 3-hour hypothermia(n=8) group, respectively. Infarct size measured at 1, 4 and 7 days after MCA occlusion was 22.2%+/-4.4%, 14.3%+/-6.6%, 13.7%+/-5.3% in the non-treated group, 19.6%+/-10.0%, 12.5%+/-6.2%, 12.0%+/-6.9% in the 2-hour hypothermia group and 12.9%+/-5.6%, 8.3%+/-3.3%, 8.2%+/-2.3% in the 3-hour hypothermia group. In the 2-hour hypothermia group, no significant size reduction was seen, but in the 3-hour hypothermia group, infarct size had decreased to half of that of the non-treated group(p<0.05). This protective effect was observed untill 1 week after MCA occlusion. rCGU in the non-treated group measured at 1 hour after MCA occlusion had increased in the periphery of the ischemic core, but at 4 hours, periischemic hypermetabolism had disappeared and the area of low metabolism in the center had become larger. rCGU in the 3-hour hypothermia group measured at 1 hour after MCA occlusion(BT 26degreesC) showed a uniform decrease in all regions, supressing temporary periischemic hypermetabolism, and at 4 hours(BT 37degreesC) after occlusion, hypermetabolism was not prominent and the area of low metabolism in the center had narrowed. This study indicates that 3 hour moderate hypothermia immediately after MCA occlusion significantly reduces infarct size, and that this protective effect was associated with suppression of periischemic hypermetabolism occurring around 1 hour after MCA occlusion.