Photobiomodulation (PBM) therapy is a promising therapeutic approach for several pathologies, including stroke. The biological effects of PBM for the treatment of cerebral ischemia have previously been explored as a neuroprotective strategy using different light sources, wavelengths, and incident light powers. However, the capability of PBM as a novel alternative therapy to stimulate the recovery of the injured neuronal tissue after ischemic stroke has been poorly explored.
View Article and Find Full Text PDFBackground: Excitatory amino acid transporter 2 (EAAT) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT for glutamate uptake, we hypothesized that the expression of this transporter in mesenchymal stem cells (MSCs) for systemic administration could yield a cell-based glutamate-grabbing therapy, combining the intrinsic properties of these cells with excitotoxic protection.
Methods: To address this hypothesis, EAAT-encoding cDNA was introduced into MSCs and human embryonic kidney 293 cells (HEK cells) as the control cell line.
Neurological diseases of diverse aetiologies have significant effects on the quality of life of patients. The limited self-repairing capacity of the brain is considered to be the origin of the irreversible and progressive nature of many neurological diseases. Therefore, neuroprotection is an important goal shared by many clinical neurologists and neuroscientists.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.
View Article and Find Full Text PDFSuperparamagnetic iron oxide nanoparticles (SPIO-PAA), ultrasmall iron oxide nanoparticles (USPIO-PAA), and glucosamine-modified iron oxide nanoparticles (USPIO-PAA-GlcN) were studied as mesenchymal stem cell (MSCs) labels for cell tracking applications by magnetic resonance imaging (MRI). Pronounced differences were found in the labeling performance of the three samples in terms of cellular dose and labeling efficiency. In combination with polylysine, SPIO-PAA showed nonhomogeneous cell internalization, while for USPIO-PAA no uptake was found.
View Article and Find Full Text PDFSuperparamagnetic iron oxide nanoparticles (MNPs) together with magnetic resonance imaging (MRI) are the preferred tools for monitoring the fate and biodistribution of administered cells in stem cell therapy studies. Commercial MNPs need transfection agents and long incubation times for sufficient cell labeling and further in vivo cell detection. In this work, we have synthesized MNPs coated with pluronic F127 and tetronic 908, and validated their applicability as contrast agents for MRI cell detection on two different cell types: rat mesenchymal stem cells (MSCs) and multipotent neural progenitor cell line from mice (C17.
View Article and Find Full Text PDFUltrasmall superparamagnetic iron oxide nanoparticles (USPIOs) coated with polyacrylic acid (PAA) were synthesized by a hydrothermal method in gram-scale quantity and extensively characterized. Only the nanoparticles subjected to an additional centrifugation step showed narrow size distribution, high polymeric coverage, and ideal superparamagnetism. In addition to improved physico-chemical properties, these nanoparticles feature high stability in vitro as well as dual T1-T2 performance as contrast agents (CAs) for magnetic resonance imaging (MRI), highlighting the importance of the additional separation step in obtaining material with the desired properties.
View Article and Find Full Text PDFGellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use.
View Article and Find Full Text PDFRecent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia.
View Article and Find Full Text PDFWe 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.
View Article and Find Full Text PDFThe use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment.
View Article and Find Full Text PDFUnlabelled: In order to provide sufficient sensibility for detection, selection of an adequate payload of imaging probe is critical, during the design of MRI theranostic nanoplatforms. This fact is particularly crucial for in vivo applications in the brain, where delivery of macromolecules is limited by the blood-brain barrier. Here we report a simple and quick process for the estimation of adequate payloads of gadolinium in liposomes with potential to act as theranostic agents, for in vivo MRI applications in the brain.
View Article and Find Full Text PDFMagnetic nanoparticle (MNP) enabled cell visualization with magnetic resonance imaging (MRI) is currently an intensively studied area of research. In the present study, we have synthesized polyethylene glycolated (PEG) MNPs and validated their suitability as MR cell labeling agents in in vitro and in vivo experiments. The labeling of therapeutic potent mesenchymal stem cells (MSCs) with small core and large core MNPs was evaluated.
View Article and Find Full Text PDFIntroduction: 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.
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.
View Article and Find Full Text PDFAs ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines.
View Article and Find Full Text PDFLiposome encapsulation of active principles enhances their bioavailability to the brain. We investigated whether encapsulation of citicoline in liposomes increases its therapeutic effects in ischemia, performing a longitudinal MRI study of lesion volumes and edema in an animal model of stroke. Nineteen rats were submitted to permanent occlusion of the middle cerebral artery and treated with: (1) saline, (2) intraperitoneal citicoline (500mg/kg), (3) intravenous citicoline (48mg/kg), and (4) intravenous liposome-encapsulated citicoline (48mg/kg).
View Article and Find Full Text PDF