ABSTRACT
The pathophysiology of ischemic stroke involves multiple events such as inflammation and oxidative stress which will lead to neuronal death and cognitive deficits. The (-)-α-bisabolol is a monocyclic sesquiterpene alcohol found in various plants and mainly in Matricaria chamomilla, which exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. The aim of this work was to investigate the neuroprotective effects of (-)-α-bisabolol in mice underwent permanent occlusion of the middle cerebral artery (pMCAO). Animals were treated with (-)-α-bisabolol (50, 100 and 200â¯mg/kg/day, orally) or vehicle (3% tween 80) one day before and 1â¯h after pMCAO and the treatment continued once daily for the following five days. The treatment with (-)-α-bisabolol (100 and 200â¯mg/kg) significantly reduced the infarcted area and neurological deficits caused by pMCAO. (-)-α-bisabolol at the 200â¯mg/kg dose increased cell viability and decreased neuronal degeneration, as evaluated by cresyl violet and Fluoro-Jade C stainings, respectively. (-)-α-bisabolol also increased the locomotor activity which was reduced by cerebral ischemia and improved pMCAO-induced working, spatial, object recognition, and aversive memories deficits. (-)-α-bisabolol (200â¯mg/kg) significantly prevented the increase of myeloperoxidase (MPO) activity, TNF-α immunoreactivity in the temporal cortex, and the increase of iNOS both in the temporal cortex and in the striatum. (-)-α-bisabolol treatment also prevented astrogliosis in these areas. These data showed that (-)-α-bisabolol provides neuroprotective action probably due to its anti-inflammatory activity, although other mechanisms cannot be discarded.
Subject(s)
Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Memory Disorders/drug therapy , Memory Disorders/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Sesquiterpenes/pharmacology , Animals , Biomarkers/metabolism , Cell Death/drug effects , Inflammation/metabolism , Male , Maze Learning/drug effects , Memory Disorders/complications , Memory Disorders/pathology , Mice , Monocyclic Sesquiterpenes , Neurons/pathology , Neuroprotective Agents/therapeutic use , Sesquiterpenes/therapeutic useABSTRACT
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...
