RESUMEN
AIM: The aim was to evaluate the beneficial effect of early mitogen-activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non-invasively for 2 weeks. METHOD: Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion. Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to evaluate cerebral perfusion at day 14. Immunohistochemistry evaluation of Ki67 was performed 14 days post-stroke. RESULTS: U0126 improved long-term behavioural outcome and significantly reduced infarct size. In addition, cerebral perfusion in U0126-treated animals was improved compared to the vehicle group. Immunohistochemistry showed a significant increase in Ki67+ cells in U0126-treated animals compared to the vehicle group. CONCLUSION: Early MEK1/2 inhibition improves long-term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.
Asunto(s)
Encéfalo/efectos de los fármacos , Butadienos/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , MAP Quinasa Quinasa 1/antagonistas & inhibidores , MAP Quinasa Quinasa 2/antagonistas & inhibidores , Imagen por Resonancia Magnética , Nitrilos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/enzimología , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/enzimología , Infarto de la Arteria Cerebral Media/fisiopatología , Antígeno Ki-67/metabolismo , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/metabolismo , Masculino , Ratas Wistar , Recuperación de la Función , Factores de TiempoRESUMEN
MRI and MRS in small rodents demand very high sensitivity. Cryogenic transmit/receive radiofrequency probes (CryoProbes) designed for (1) H MRI of mouse brain provide an attractive option for increasing the performance of small-animal MR systems. As the Larmor frequency of (13) C nuclei is four times lower than that for (1) H nuclei, an even larger sensitivity improvement is expected for (13) C applications. The aim of this work was to evaluate the performance of a prototype (13) C CryoProbe™ for mouse brain MRS. To investigate the possible gain of the (13) C CryoProbe™, we acquired localized single-voxel (13) C spectra and chemical shift images of a dimethyl sulfoxide phantom with the CryoProbe™, as well as with two room temperature resonators. The cryogenically cooled resonator achieved approximately four-fold higher signal-to-noise ratio in phantom tests when compared with the best-performing room temperature coil. In addition, we present localized (13) C spectra of mouse brain obtained with the CryoProbe™, as well as with one of the room temperature coils, demonstrating the performance in vivo. In summary, the cryogenic cooling technique significantly enhances the (13) C signal sensitivity at 9.4 T and enables the investigation of metabolism within mouse brain.
Asunto(s)
Encéfalo/metabolismo , Isótopos de Carbono , Espectroscopía de Resonancia Magnética/instrumentación , Relación Señal-Ruido , Animales , Glucosa/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Ratones , Ratones Endogámicos C57BL , Fantasmas de Imagen , TemperaturaRESUMEN
The non-invasive localization of focal heart activity via body surface potential measurements (BSPM) could greatly benefit the understanding and treatment of arrhythmic heart diseases. However, the in vivo validation of source localization algorithms is rather difficult with currently available measurement techniques. In this study, we used a physical torso phantom composed of different conductive compartments and seven dipoles, which were placed in the anatomical position of the human heart in order to assess the performance of the Recursively Applied and Projected Multiple Signal Classification (RAP-MUSIC) algorithm. Electric potentials were measured on the torso surface for single dipoles with and without further uncorrelated or correlated dipole activity. The localization error averaged 11 +/- 5 mm over 22 dipoles, which shows the ability of RAP-MUSIC to distinguish an uncorrelated dipole from surrounding sources activity. For the first time, real computational modelling errors could be included within the validation procedure due to the physically modelled heterogeneities. In conclusion, the introduced heterogeneous torso phantom can be used to validate state-of-the-art algorithms under nearly realistic measurement conditions.