2,3-Dihydro-1-benzofuran-5-ols as Analogs of .alpha.-Tocopherol That Inhibit in Vitro and ex Vivo Lipid Autoxidation and Protect Mice against Central Nervous System Trauma

1995 ◽  
Vol 38 (3) ◽  
pp. 453-458 ◽  
Author(s):  
J. Martin Grisar ◽  
Frank N. Bolkenius ◽  
Margaret A. Petty ◽  
Joelle Verne
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ex Vivo ◽  
Alpha Tocopherol ◽  
Lipid Autoxidation ◽  
Central Nervous System Trauma

scholarly journals Human autoantibodies to amphiphysin induce defective presynaptic vesicle dynamics and composition

Brain ◽  
2015 ◽  
Vol 139 (2) ◽  
pp. 365-379 ◽  
Author(s):  
Christian Werner ◽  
Martin Pauli ◽  
Sören Doose ◽  
Andreas Weishaupt ◽  
Holger Haselmann ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ex Vivo ◽  
Super Resolution ◽  
Synaptic Activity ◽  
Stiff Person Syndrome ◽  
Specific Patient ◽  
Presynaptic Boutons ◽  
Presynaptic Vesicle

Abstract See Irani (doi:10.1093/awv364) for a scientific commentary on this article.  Stiff-person syndrome is the prototype of a central nervous system disorder with autoantibodies targeting presynaptic antigens. Patients with paraneoplastic stiff-person syndrome may harbour autoantibodies to the BAR (Bin/Amphiphysin/Rvs) domain protein amphiphysin, which target its SH3 domain. These patients have neurophysiological signs of compromised central inhibition and respond to symptomatic treatment with medication enhancing GABAergic transmission. High frequency neurotransmission as observed in tonic GABAergic interneurons relies on fast exocytosis of neurotransmitters based on compensatory endocytosis. As amphiphysin is involved in clathrin-mediated endocytosis, patient autoantibodies are supposed to interfere with this function, leading to disinhibition by reduction of GABAergic neurotransmission. We here investigated the effects of human anti-amphiphysin autoantibodies on structural components of presynaptic boutons ex vivo and in vitro using electron microscopy and super-resolution direct stochastic optical reconstruction microscopy. Ultrastructural analysis of spinal cord presynaptic boutons was performed after in vivo intrathecal passive transfer of affinity-purified human anti-amphiphysin autoantibodies in rats and revealed signs of markedly disabled clathrin-mediated endocytosis. This was unmasked at high synaptic activity and characterized by a reduction of the presynaptic vesicle pool, clathrin coated intermediates, and endosome-like structures. Super-resolution microscopy of inhibitory GABAergic presynaptic boutons in primary neurons revealed that specific human anti-amphiphysin immunoglobulin G induced an increase of the essential vesicular protein synaptobrevin 2 and a reduction of synaptobrevin 7. This constellation suggests depletion of resting pool vesicles and trapping of releasable pool vesicular proteins at the plasma membrane. Similar effects were found in amphiphysin-deficient neurons from knockout mice. Application of specific patient antibodies did not show additional effects. Blocking alternative pathways of clathrin-independent endocytosis with brefeldin A reversed the autoantibody induced effects on molecular vesicle composition. Endophilin as an interaction partner of amphiphysin showed reduced clustering within presynaptic terminals. Collectively, these results point towards an autoantibody-induced structural disorganization in GABAergic synapses with profound changes in presynaptic vesicle pools, activation of alternative endocytic pathways, and potentially compensatory rearrangement of proteins involved in clathrin-mediated endocytosis. Our findings provide novel insights into synaptic pathomechanisms in a prototypic antibody-mediated central nervous system disease, which may serve as a proof-of-principle example in this evolving group of autoimmune disorders associated with autoantibodies to synaptic antigens.

Encapsulated Mesenchymal Stem Cells for Central Nervous System Repair

2010 ◽  
Author(s):  
Jeffrey Barminko ◽  
Jean Pierre Dolle ◽  
Rene Schloss ◽  
Martin Grumet ◽  
Martin L. Yarmush
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protective Role ◽  
Treatment Processes ◽  
Therapeutic Benefits ◽  
Central Nervous System Trauma ◽  
A Cell ◽  
End Stage ◽  
Central Nervous System Repair

Mesenchymal stromal cells (MSC) have long been regarded as a cell source with the potential to provide therapies for various different tissue pathologies. They were originally identified for their ability to adhere to tissue culture plastic and gained favor due to their tremendous ability to propagate[1]. It was this finding as well as their ability to differentiate into lineages of mesoderm which have long made MSC a potential tool for autologous cellular replacement therapies [2, 3]. More recently, their cyto-protective role has been realized and been implicated in the benefit achieved in treating various different tissue pathologies. MSC have been found to secrete several different cytokines and growth factors in vitro. Furthermore, these factors can be modulated based on the environment MSC are exposed to. MSC have shown therapeutic benefits in models of GVHD, myocardial infarction, fulminant hepatic failure, central nervous system trauma and others, without any apparent cellular replacement. These advances propelled MSC to the fore front of potential cellular therapies and many are seeking to take advantage of their tissue protective properties. However, several draw backs in current methods of MSC implantation limit the ability to carry out safe and controlled clinical trials. Limitation with current MSC implantation approaches include; 1) directly transplanted MSCs exposed to the complex injury environment may be affected themselves early in the treatment processes, 2) MSC may also migrate to undesired tissue locations and 3) may differentiate into undesired end stage cells. These issues severally limit the translatability of MSC treatments in clinical settings; they make controlling experiments very difficult. There becomes a need to develop engineered methods for delivering these cells in a controlled manner. In order to circumvent these potential problems, we propose to use an alginate microencapsulation system as a vehicle for MSC delivery taking advantage of the soluble factors MSC provide.

scholarly journals Adult mouse retina explants: an ex vivo window to explore central nervous system diseases

2020 ◽  
Author(s):  
Julia Schaeffer ◽  
Celine Tardy ◽  
Floriane Albert ◽  
Stephane Belin ◽  
Homaira Nawabi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Axon Regeneration ◽  
Ex Vivo ◽  
Adult Retina ◽  
Cellular Events ◽  
Embryonic Neurons

ABSTRACTWhen the developing central nervous system (CNS) becomes mature, it loses its ability to regenerate. Therefore, any insult to adult CNS leads to a permanent and irreversible loss of motor and cognitive functions. For a long time, much effort has been deployed to uncover mechanisms of axon regeneration in the CNS. It is now well understood that neurons themselves lose axon regeneration capabilities during development, and also after a lesion or in pathological conditions. Since then, many molecular pathways such as mTOR and JAK/STAT have been associated with axon regeneration. However, no functional recovery has been achieved yet. Today, there is a need not only to identify new molecules implicated in adult CNS axon regeneration, but also to decipher the fine molecular mechanisms associated with regeneration failure. This is critical to make progress in our understanding of neuroprotection and neuroregeneration and for the development of new therapeutic strategies. In this context, it remains particularly challenging to address molecular mechanisms in in vivo models of CNS regeneration. The extensive use of embryonic neurons as in vitro model is a source of bias, as they have the intrinsic competence to grow their axon upon injury, unlike mature neurons. In addition, this type of dissociated neuronal cultures lack a tissue environment to recapitulate properly molecular and cellular events in vitro. Here, we propose to use cultures of adult retina explants to fill this gap. The visual system - which includes the retina and optic nerve - is a gold-standard model to study axon regeneration and degeneration in the mature CNS. Cultures of adult retina explants combine two advantages: they have the simplicity of embryonic neurons cultures and they recapitulate all the aspects of in vivo features in the tissue. Importantly, it is the most appropriate tool to date to isolate molecular and cellular events of axon regeneration and degeneration of the adult CNS in a dish. This ex vivo system allows to set up a large range of experiments to decipher the fine molecular and cellular regulations underlying mature CNS axon growth.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

scholarly journals Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Delivery System ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Health Priorities ◽  
The Central Nervous System ◽  
Vitro Release ◽  
Dual Drug

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.

scholarly journals Absence of the αvβ3 Integrin Dictates the Time-Course of Angiogenesis in the Hypoxic Central Nervous System: Accelerated Endothelial Proliferation Correlates with Compensatory Increases in α5β1 Integrin Expression

2010 ◽  
Vol 30 (5) ◽  
pp. 1031-1043 ◽  
Author(s):  
Longxuan Li ◽  
Jennifer V Welser ◽  
Richard Milner
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Time Course ◽  
Αvβ3 Integrin ◽  
Integrin Expression ◽  
Brain Endothelial Cells ◽  
Endothelial Proliferation ◽  
Β3 Integrin ◽  
Α5β1 Integrin

Cerebral angiogenesis is an important adaptive response to hypoxia. As the αvβ3 integrin is induced on angiogenic vessels in the ischemic central nervous system (CNS), and the suggested angiogenic role for this integrin in other systems, it is important to determine whether the αvβ3 integrin is an important mediator of cerebral angiogenesis. αvβ3 integrin expression was examined in a model of cerebral hypoxia, in which mice were subject to hypoxia (8% O2) for 0, 4, 7, or 14 days. Immunofluorescence and western blot analysis revealed that in the hypoxic CNS, αvβ3 integrin was strongly induced on angiogenic brain endothelial cells (BEC), along with its ligand vitronectin. In the hypoxia model, β3 integrin-null mice showed no obvious defect in cerebral angiogenesis. However, early in the angiogenic process, BEC in these mice showed an increased mitotic index that correlated closely with increased α5 integrin expression. In vitro experiments confirmed α5 integrin upregulation on β3 integrin-null BEC, which also correlated with increased BEC proliferation on fibronectin. These studies confirm hypoxic induction of αvβ3 integrin on angiogenic vessels, but suggest distinct roles for the BEC integrins αvβ3 and α5β1 in cerebral angiogenesis, with αvβ3 having a nonessential role, and α5β1 promoting BEC proliferation.

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