RESUMEN
PURPOSE: To examine the effects of hyperbaric oxygen (HBO) therapy and knockout of toll-like receptor 4 (TLR4) on the outcome of temporary middle cerebral artery occlusion (MCAO) in a mouse model. MATERIALS AND METHODS: MCAO was induced in anesthetized male C57Bl/6 mice (WT) and TLR4 knockout mice (TLR4(-/-)) using an intra-arterial filament method. After 30 or 90 min, the filament was removed, and the mice were given either no treatment (WT and TLR4(-/-) groups) or HBO (WT only). Mice were euthanized 24 h after MCAO, and the brain infarct area was examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: In the WT group, without treatment, lesion volume was 120 ± 13 mm(3) in the mice subjected to 30 min' MCAO and 173 ± 23 mm(3) in the mice subjected to 90 min' MCAO. Respective values with HBO treatment were 66.5 ± 36.7 mm(3) and 53.2 ± 17.2 mm(3). The difference was significant only for 90-minute MCAO (p < 0.01, nonparametric test). In the TLR4(-/-) group (all untreated), lesion volume was 95.9 ± 17.9 after 90 min of MCAO, which was significantly lower than in the untreated WT animals (p < 0.05, nonparametric test). CONCLUSIONS: A single treatment of HBO immediately after MCAO followed by 24 h' reperfusion significantly reduces edema and may improve perfusion. TLR4 knockout protects mice from MCAO damage, but to a lesser extent than HBO treatment.
Asunto(s)
Citocinas/metabolismo , Oxigenoterapia Hiperbárica , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/terapia , Receptor Toll-Like 4/deficiencia , Animales , Edema Encefálico/etiología , Edema Encefálico/terapia , Citocinas/genética , Modelos Animales de Enfermedad , Lateralidad Funcional/efectos de los fármacos , Lateralidad Funcional/genética , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Infarto de la Arteria Cerebral Media/mortalidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Reperfusión/métodos , Estadísticas no Paramétricas , Receptor Toll-Like 4/genéticaRESUMEN
To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n = 7) received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n = 16), total stroke volume was 19.20 ± 6.38 mm(3), mean penumbra area was 4.5 ± 2.03 mm(3), and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n = 19) were 17.79 ± 5.80 mm(3), 7.3 ± 3.5 mm(3), and 108.6%; in the delayed (6 h) bevacizumab injected mice (n = 7) they were 9.80 ± 8.00 mm(3), 2.4 ± 2.0 mm(3), and 98.2%; and in the sildenafil group (n = 16) they were 18.42 ± 5.41 mm(3), 5.7 ± 2.02 mm(3), and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p = 0.03) and sildenafil-treated (p = 0.003) groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.