Analysis of the Impact of CD200 on Neurodegenerative Diseases

Neuroinflammation, accompanied by neuronal loss and dysfunction, is a characteristic of neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD). It is well documented that inappropriate activation of glia is the primary cause of neuroinflammation (Masocha, 2009), but their role in the pathogenesis of neurodegenerative diseases is not known. However it is certainly the case that dying neurons act to stimulate glia since they release alarmins which activate pathogen recognition receptors (PRR) and therefore the possibility exists that activation of glia especially microglia, may be a consequence, rather than a cause, of neurodegenerative processes which characterize diseases like AD and PD. Understanding microglial function remains a major goal since it is widely believed that modulating glial function will provide a possible strategy for limiting the progression of neurodegenerative diseases. Consequently it is imperative to increase our understanding of the factors which control microglial function and the mechanisms by which expression of these factors are controlled

Non-invasive electrical brain stimulation: from acute to late-stage treatment of central nervous system damage

Non-invasive brain current stimulation (NIBS) is a promising and versatile tool for inducing neuroplasticity, protection and functional rehabilitation of damaged neuronal systems. It is technically simple, requires no surgery, and has significant beneficial effects. However, there are various technical approaches for NIBS which influence neuronal networks in significantly different ways. Transcranial direct current stimulation (tDCS), alternating current stimulation (ACS) and repetitive transcranial magnetic stimulation (rTMS) all have been applied to modulate brain activity in animal experiments under normal and pathological conditions. Also clinical trials have shown that tDCS, rTMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms. The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task, such as current type and strength, timing, distribution of current densities and electrode position. In this review, we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration, motor rehabilitation and cognitive enhancement

Brain targeting delivery facilitated by ligand-functionalized layered double hydroxide nanoparticles

A delivery platform with highly selective permeability through blood brain barrier (BBB) is essential for brain disease treatment. In this research, we designed and prepared a novel target nano-platform, i.e. layered double hydroxide nanoparticle (LDH) conjugated with targeting peptide-ligand angiopep2 (Ang2) or rabies virus glycoprotein (RVG) via inter-matrix bovine serum albumin (BSA) for brain targeting. In vitro studies show that functionalization with the target ligand significantly increases the delivery efficiency of LDH nanoparticles to the brain endothelial cells (bEnd.3) and the transcytosis through the simulated BBB model, i.e. bEnd.3 cell-constructed multilayer membrane. In vivo confocal neuroimaging (ICON) of the rat's blood-retina area dynamically demonstrates that LDH nanoparticles modified with peptide ligands have shown a prolonged retention period within the retina vessel in comparison with pristine LDH group. Moreover, Ang2-modified LDH nanoparticles are found to more specifically accumulate in the mouse brain than the control and RGV-modified LDH nanoparticles after 2 and 48 h intravenous injection. All these findings strongly suggest that Ang2-modified LDHs can serve as an effective targeting nano-platform for brain disease treatment

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Abstract Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions

The blood-brain barrier and beyond: Nano-based neuropharmacology and the role of extracellular matrix

Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1) outline the state-of-the art knowledge on BBB passage, 2) address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3) highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nanosystem with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease

Vision modulation, plasticity and restoration using non-invasive brain stimulation – an IFCN-sponsored review

The visual system has one of the most complex structures of all sensory systems and is perhaps the most important sense for everyday life. Its functional organization was extensively studied for decades in animal and humans, for example by correlating circumscribed anatomical lesions in patients with the resulting visual dysfunction. During the past two decades, significant achievements were accomplished in characterizing and modulating visual information processing using non-invasive stimulation techniques of the normal and damaged human eye and brain. Techniques include transcranial magnetic stimulation (TMS) and low intensity electric stimulation using either direct or alternating currents applied transcranially (tDCS or tACS) near or above the visual cortex, or alternating currents applied transorbitally (trACS). In the case of transorbital stimulation of the visual system the electrodes are attached near the eye, to the eyelids (transpalpebral electrical stimulation – TPES) or the cornea (tanscorneal electrical stimulation TcES). Here, we summarize the state-of-the-art of visual system magnetic and electric stimulation as a method to modulate normal vision, induce brain plasticity, and to restore visual functions in patients. We review this field’s history, models of current flow paths in the eye and brain, neurophysiological principles (e.g. entrainment and after-effects), the effects on vision in normal subjects and the clinical impact on plasticity and vision restoration in patients with low vision, with a particular focus on “off-line” or “after-effects”. With regard to the therapeutic possibilities, ACS was demonstrated to be effective in patients affected by glaucoma and optic neuropathy, while tDCS and random noise stimulation (tRNS) are most promising for the treatment of amblyopia, hemianopia and myopia. In addition, rTMS applied above the occipital area is a promising approach to treat migraine, neglect and hemianopia. Although the response to these treatment options is better than to sham stimulation in double blinded clinical studies, the clinical efficacy is still rather variable and a proportion of patients do not respond. It is therefore imperative to better understand the mechanisms of action to be able to optimize treatment protocols possibly through personalization of brain stimulation protocols. By identifying the current opportunities and challenges in the field, we hope to provide insights to help improve neuromodulation protocols to restore visual function in patients with visual system damage