NIR-light active hybrid nanoparticles for combined imaging and bimodal therapy of cancerous cells.

We report the synthesis of a multifunctional biocompatible theranostic nanoplatform consisting of a biodegradable PLGA matrix surface-functionalized with indocyanine green (ICG), a near-IR fluorescent dye, and co-loaded with superparamagnetic iron oxide nanoparticles (SPIONs) and the anticancer drug doxorubicin (DOXO). Combination of chemo- and photothermal therapeutic efficacy as well as magnetic resonance and optical fluorescence imaging performance were successfully tested in vitro on a tumoral cervical HeLa cell line. Magnetic in vitro guided targeting of these nanoplatforms was also proven. These nanoconstructs also enabled to monitor their in vivo biodistribution by fluorescence imaging in a mice model, which revealed their effective accumulation in the tumor and, unexpectedly, in the brain area. A lower presence of nanoplatforms was noted in the reticulo-endothelial system. The present observations suggest the nanoplatforms ability to possibly overcome the blood brain barrier. These results open up new possibilities to use our multifunctional nanoplatforms to treat brain-located diseases.

Comparación de la lesión producida en tres modelos animales de isquemia cerebral focal permanente mediante resonancia magnética / Comparison of the lesion produced by permanent focal cerebral ischaemia in three animal models using magnetic resonance imaging

Introducción. Los modelos animales de isquemia cerebral son indispensables en la investigación de la patología cerebrovascular. Actualmente, no existe un modelo experimental que refleje perfectamente la fisiopatología del ictus, por lo que la selección de éste es fundamental para una interpretación correcta de los resultados obtenidos. Objetivo. Caracterizar la evolución temporal de tres modelos comunes de isquemia cerebral focal permanente mediante resonancia magnética. Materiales y métodos. Treinta ratas macho Sprague-Dawley se dividieron en tres grupos, cada uno sometido a los siguientes modelos quirúrgicos: sutura intracraneal de la arteria cerebral media (ACM), electrocoagulación de la ACM y oclusión intraluminal de la ACM. Cada animal se sometió a una exploración por resonancia magnética los días 1, 2, 3, 4, 7 y 14 tras la cirugía. A partir de imágenes adquiridas con secuencias potenciadas en T2 se calcularon tanto el volumen de lesión como el grado de edema. Resultados. El modelo intraluminal presentó mayor volumen de infarto (media: 297 ± 163 mm3 de volumen máximo) y mayor edema (media: 17 ± 9% de edema máximo) frente al modelo de sutura intracraneal (178 ± 62 mm3 y 9 ± 6%, respectivamente) y electrocoagulación (181 ± 45 mm3 y 9 ± 6%, respectivamente). Discusión. Pese a presentar una mayor mortalidad (28%), el modelo de oclusión intraluminal de la ACM es el más adecuado para estudios a largo plazo al no precisar craneotomía, al contrario que los modelos transcraneales. El modelo de oclusión por electrocoagulación muestra una región cerebral de lesión no isquémica y una evolución de la lesión diferente a los otros dos modelos (AU)

Introduction. Animal models of brain ischemia are essential to reveal the full aspects of cerebrovascular pathologies. The perfect animal model that reflects every aspect of stroke pathophysiology does not exist, hence there is a need for a proper selection of the animal model in order to interpret properly the results from experimental research. Aim. To characterize and compare the temporal evolution of three common models of focal brain ischemia using magnetic resonance imaging (MRI) techniques. Materials and methods. Thirty Sprague-Dawley rats were distributed into three groups, each of them submitted to one of the following surgery procedures: middle cerebral artery (MCA) intracranial suture, MCA electrocoagulation, and MCA intraluminal suture. Each rat was subjected to an MRI study at days 1, 2, 3, 4, 7 and 14 post-surgery. T2 weighted images were obtained in order to calculate both lesion volumes and edema. Results. Infarct volume and edema were maximal for the intraluminal model (peaks of mean 297 ± 163 mm3 and mean 17 ± 9%, respectively) compared to intracranial suture (178 ± 62 mm3 and 9 ± 6%, respectively) and electrocoagulation (181 ± 45 mm3 and 9 ± 6%, respectively) models. Discussion. The intraluminal occlusion of the MCA model, although yields in the highest mortality rate (28%), it is the more suitable for long term studies, mainly because of the absence of craniotomy. In the electrocoagulation model a non ischemic lesion region is observed which leads to an abnormal lesion evolution as compared with the other two models (AU)

[Comparison of the lesion produced by permanent focal cerebral ischaemia in three animal models using magnetic resonance imaging]. / Comparacion de la lesion producida en tres modelos animales de isquemia cerebral focal permanente mediante resonancia magnetica.

INTRODUCTION: Animal models of brain ischemia are essential to reveal the full aspects of cerebrovascular pathologies. The perfect animal model that reflects every aspect of stroke pathophysiology does not exist, hence there is a need for a proper selection of the animal model in order to interpret properly the results from experimental research. AIM: To characterize and compare the temporal evolution of three common models of focal brain ischemia using magnetic resonance imaging (MRI) techniques. MATERIALS AND METHODS: Thirty Sprague-Dawley rats were distributed into three groups, each of them submitted to one of the following surgery procedures: middle cerebral artery (MCA) intracranial suture, MCA electrocoagulation, and MCA intraluminal suture. Each rat was subjected to an MRI study at days 1, 2, 3, 4, 7 and 14 post-surgery. T2 weighted images were obtained in order to calculate both lesion volumes and edema. RESULTS: Infarct volume and edema were maximal for the intraluminal model (peaks of mean 297 ± 163 mm3 and mean 17 ± 9%, respectively) compared to intracranial suture (178 ± 62 mm3 and 9 ± 6%, respectively) and electrocoagulation (181 ± 45 mm3 and 9 ± 6%, respectively) models. DISCUSSION: The intraluminal occlusion of the MCA model, although yields in the highest mortality rate (28%), it is the more suitable for long term studies, mainly because of the absence of craniotomy. In the electrocoagulation model a non ischemic lesion region is observed which leads to an abnormal lesion evolution as compared with the other two models.

[Imaging techniques for studying functional recovery following a stroke: I. Methodological aspects]. / Tecnicas de imagen para el estudio de la recuperacion funcional tras el ictus: I. Aspectos metodologicos.

Many patients that survive stroke have to face serious functional disabilities for the rest of their lives, which is a personal drama for themselves and their relatives, and an elevated charge for society. Thus functional recovery following stroke should be a key objective for the development of new therapeutic approaches. In this series of two works we review the strategies and tools available nowadays for the evaluation of multiple aspects related to brain function (both in humans and research animals), and how they are helping neuroscientist to better understand the processes of restoration and reorganization of brain function that are triggered following stroke. We have mainly focused on magnetic resonance applications, probably the most versatile neuroimaging technique available nowadays, and that everyday surprises us with new and exciting applications. But we tackle other alternative and complementary techniques, since a multidisciplinary approach allows a wider perspective over the underlying mechanisms behind tissue repair, plastic reorganization of the brain and compensatory mechanisms that are triggered after stroke. The first of the works of this series is focused on methodological aspects that will help us to understand how it is possible to assess brain function based on different physical and physiological principles. In the second work we will focus on different practical issues related to the application of the techniques here discussed.