Potential Role of Exosomes in Ischemic Stroke Treatment

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.

An Innovative In Vitro Open-Angle Glaucoma Model (IVOM) Shows Changes Induced by Increased Ocular Pressure and Oxidative Stress

Primary Open-Angle Glaucoma (POAG) is a neurodegenerative disease, and its clinical outcomes lead to visual field constriction and blindness. POAG’s etiology is very complex and its pathogenesis is mainly explained through both mechanical and vascular theories. The trabecular meshwork (TM), the most sensitive tissue of the eye anterior segment to oxidative stress (OS), is the main tissue involved in early-stage POAG, characterized by an increase in pressure. Preclinical assessments of neuroprotective drugs on animal models have not always shown correspondence with human clinical studies. In addition, intra-ocular pressure management after a glaucoma diagnosis does not always prevent blindness. Recently, we have been developing an innovative in vitro 3Dadvanced human trabecular cell model on a millifluidicplatform as a tool to improve glaucoma studies. Herein, we analyze the effects of prolonged increased pressure alone and, in association with OS, on such in vitro platform. Moreover, we verify whethersuch damaged TM triggers apoptosis on neuron-like cells. The preliminary results show that TM cells are less sensitive to pressure elevation than OS, and OS-damaging effects were worsened by the pressure increase. The stressed TM releases harmful signals,which increase apoptosis stimuli on neuron-like cells, suggesting its pivotal role in the glaucoma cascade.

Neuroprotective Effects of Propylgallate Against Oxidative Stress in Retinal Ganglion Cells

Background: Diabetic retinopathy is a group of eye diseases which result in damage to the optic nerve and vision loss, it has seriously affect peoples' health. The purpose of this study is to contrast the neuroprotective effects of curcumin, gastrodin, propylgallate, adenosine. At the same time, we preliminarily explore the molecular mechanism of protective drugs.Methods: In this study, we used 500μM H2O2 treated RGC-5 cells to induce a cellular oxidative stress model. We treated this cell model with four drug monomers: Propylgallate, Curcumin, Gastrodin and Adenosine to find drug monomers with neuroprotective effect. We used apoptosis PCR array to obtain apoptosis related genes regulated by neuroprotective drugs.Results: We found the Propylgallate treated RGC-5 cells had highest survival rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.In addition, it had lowest cell cytotoxicity and apoptotic rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.Moreover, the expression of ROS in Propylgallate treated RGC-5 cells was lowest when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells. We found that Caspase-3, Caspase-8, and Caspase-9 are the main target genes of Propylgallate which can preliminarily explain the neuroprotective mechanism of Propylgallate against apoptosis..Conclusion: The present study revealed that the propylgallate has best neuroprotective effects, it may provide a promissing drug to prevent and improve the damage of optic nerve. In this article, we also preliminarily expounded the neuroprotective molecular mechanism of Propylgallate.

Computational drug repositioning for ischemic stroke: neuroprotective drug discovery

Background: A comprehensive approach to drug repositioning will be required to overcome translational hurdles and identify more neuroprotective drugs. Results & methods: Gene Set Enrichment Analysis was applied to identify related pathways and enriched genes. Candidate genes were optimized using ToppGene, ToppGenet and pBRIT. From the perspective of the local structures, gene–domain–substructure–drug relationships were constructed. Using the MCODE algorithm and K-means clustering, 31 functional subnetworks were obtained, and 252 drugs with proposed neuroprotective function were identified. Using computational analysis, 72 substructures with different scores were found to correspond to neuroprotective functions. The protective effects of benidipine and barnidipine were confirmed in vitro. Conclusion: The authors' research has great potential to discover more neuroprotective drugs and obtain more information regarding mechanisms of action and functional substructures.

Neurodegeneration in Multiple Sclerosis: Symptoms of Silent Progression, Biomarkers and Neuroprotective Therapy—Kynurenines Are Important Players

Neurodegeneration is one of the driving forces behind the pathogenesis of multiple sclerosis (MS). Progression without activity, pathopsychological disturbances (cognitive impairment, depression, fatigue) and even optic neuropathy seems to be mainly routed in this mechanism. In this article, we aim to give a comprehensive review of the clinical aspects and symptomology, radiological and molecular markers and potential therapeutic targets of neurodegeneration in connection with MS. As the kynurenine pathway (KP) was evidenced to play an important role in the pathogenesis of other neurodegenerative conditions (even implied to have a causative role in some of these diseases) and more and more recent evidence suggest the same central role in the neurodegenerative processes of MS as well, we pay special attention to the KP. Metabolites of the pathway are researched as biomarkers of the disease and new, promising data arising from clinical evaluations show the possible therapeutic capability of KP metabolites as neuroprotective drugs in MS. Our conclusion is that the kynurenine pathway is a highly important route of research both for diagnostic and for therapeutic values and is expected to yield concrete results for everyday medicine in the future.

New Approaches in Nanomedicine for Ischemic Stroke

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient’s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapies.