RESUMO
Flavonoids have known anti-inflammatory and antioxidative actions, and they have been described as neuroprotective and able to reduce damage in CNS diseases. We evaluated the action of the flavonoid rutin in an animal model of focal cortical ischemia induced by unilateral thermocoagulation of superficial blood vessels of motor (M1) and somatosensory (S1) primary cortices. Ischemic rats were submitted to daily injections (i.p.) for five days, starting immediately after induction of ischemia. We tested two doses: 50mg/kg or 100mg/kg of body weight. Sensorimotor tests were used to evaluate functional recovery. Bioavailability in plasma was done by chromatographic analysis. The effect of treatment in lesion volume and neurodegeneration was evaluated 48 h and 72 h after ischemia, respectively. We observed significant sensorimotor recovery induced by rutin, and the dose of 50mg/kg had more pronounced effect. Thus, this dose was used in further analyses. Plasma availability of rutin was detected from 2h to at least 8h after ischemia. The treatment did not result in reduction of lesion volume but reduced the number of degenerated neurons at the periphery of the lesion. The results suggest rutin as an efficient drug to treat brain ischemia since it was able to promote significant recovery of sensorimotor loss, which was correlated to the reduction of neurodegeneration in the periphery of cortical injury. Increasing studies with rutin and other flavonoids might give support for further clinical trials with these drugs.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Córtex Cerebral/patologia , Fármacos Neuroprotetores/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Rutina/uso terapêutico , Análise de Variância , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fluoresceínas , Masculino , Força Muscular/efeitos dos fármacos , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Rutina/sangue , Rutina/farmacologia , Fatores de TempoRESUMO
Previous studies have shown sensorimotor recovery by treatment with bone marrow mononuclear cells (BMMCs) after focal brain ischemia. However, sensorimotor tests commonly used are designed to examine motor patterns that do not involve skill or training. We evaluated whether BMMCs treatment was able to recover forelimb skilled movements. Reaching chamber/pellet retrieval (RCPR) task was used, in which animals had to learn to grasp a single food pellet and lead it to its mouth. We also evaluated therapeutic effect of this training on unskilled sensorimotor function. Adult male Wistar rats suffered unilateral cortical ischemia by thermocoagulation in motor and somesthetic primary areas. A day later, they received i.v. injection of 3×10(7) BMMCs or vehicle (saline), forming four experimental groups: BMMCs+RCPR; saline+RCPR; BMMCs and saline. Cylinder and adhesive tests were applied in all experimental groups, and all behavioral tests were performed before and along post-ischemic weeks after induction of ischemia. Results from RCPR task showed no significant difference between BMMCs+RCPR and saline+RCPR groups. In cylinder test, BMMCs-treated groups showed significant recovery, but no significant effect of RCPR training was observed. In adhesive test, BMMCs treatment promoted significant recovery. Synergistic effect was found since only together they were able to accelerate recovery. The results showed that BMMCs treatment promoted increased recovery of unsophisticated sensorimotor function, but not of skilled forepaw movements. Thus, BMMCs might not be able to recover all aspects of sensorimotor functions, although further studies are still needed to investigate this treatment in ischemic lesions with different locations and extensions.