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axonal repair

Christine D Plant, Giles W Plant
Schwann cells are the primary inducers of regeneration of the peripheral nervous system. Schwann cells can be isolated from adult peripheral nerves, expanded in large numbers, and genetically transduced by viral vectors in vitro prior to their use in vivo. Here we describe how to use lentiviral vectors to transduce primary Schwann cells in vitro. We also describe how cultured Schwann cells can be used in conjunction with decellularized peripheral nerve sheaths prepared by multiple freeze thawing of peripheral nerve tissue...
2018: Methods in Molecular Biology
Ying Dai, Caitlin E Hill
Adult Schwann cells (SCs) can provide both a permissive substrate for axonal growth and a source of cells to ensheath and myelinate axons when transplanted into the injured spinal cord. Multiple studies have demonstrated that SC transplants can be used as part of a combinatorial approach to repairing the injured spinal cord. Here, we describe the protocols for collection and transplantation of adult rat primary SCs into the injured spinal cord. Protocols are included for the tissue culture procedures necessary for collection, quantification, and suspension of the cells for transplantation and for the surgical procedures for spinal cord injury at thoracic level nine (T9), reexposure of the injury site for delayed transplantation, and injection of the cells into the spinal cord...
2018: Methods in Molecular Biology
Xin-Peng Dun, David B Parkinson
Injury to the peripheral nervous system triggers a series of well-defined events within both neurons and the Schwann cells to allow efficient axonal regeneration, remyelination, and functional repair. The study of these events has previously been done using sections of nerve material to analyze axonal regrowth, cell migration, and immune cell infiltration following injury. This approach, however, has the obvious disadvantage that it is not possible to follow, for instance, the path of regenerating axons in three dimensions within the nerve trunk or the nerve bridge...
2018: Methods in Molecular Biology
Tanchen Ren, Anne Faust, Yolandi van der Merwe, Bo Xiao, Scott Johnson, Apoorva Kandakatla, Vijay S Gorantla, Stephen F Badylak, Kia M Washington, Michael B Steketee
In peripheral nerve (PN) injuries requiring surgical repair, as in PN transection, cellular and ECM remodeling at PN epineurial repair sites is hypothesized to reduce PN functional outcomes by slowing, misdirecting, or preventing axons from regrowing appropriately across the repair site. Herein this study reports on deriving and analyzing fetal porcine urinary bladder extracellular matrix (fUB-ECM) by vacuum assisted decellularization, fabricating fUBM-ECM nerve wraps, and testing fUB-ECM nerve wrap biocompatibility and bioactivity in a trigeminal, infraorbital nerve (ION) branch transection and direct end-to-end repair model in rat...
March 14, 2018: Scientific Reports
Junhao Deng, Yiling Zhang, Yong Xie, Licheng Zhang, Peifu Tang
Spinal cord injury (SCI) is an intractable and worldwide difficult medical challenge with limited treatments. Neural stem/progenitor cell (NS/PC) transplantation derived from fetal tissues or embryonic stem cells (ESCs) has demonstrated therapeutic effects via replacement of lost neurons and severed axons and creation of permissive microenvironment to promote repair of spinal cord and axon regeneration but causes ethnical concerns and immunological rejections as well. Thus, the implementation of induced pluripotent stem cells (iPSCs), which can be generated from adult somatic cells and differentiated into NS/PCs, provides an effective alternation in the treatment of SCI...
2018: Stem Cells International
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
Lili Zhang, Zhaomin Fan, Yuechen Han, Lei Xu, Wenwen Liu, Xiaohui Bai, Meijuan Zhou, Jianfeng Li, Haibo Wang
Valproic acid (VPA), a medication primarily used to treat epilepsy and bipolar disorder, has been applied to the repair of central and peripheral nervous system injury. The present study investigated the effect of VPA on functional recovery, survival of facial motor neurons (FMNs), and expression of proteins in rats after facial nerve trunk transection by functional measurement, Nissl staining, TUNEL, immunofluorescence, and Western blot. Following facial nerve injury, all rats in group VPA showed a better functional recovery, which was significant at the given time, compared with group NS...
March 12, 2018: Journal of Molecular Neuroscience: MN
Reza Naeimi, Fatemeh Safarpour, Mona Hashemian, Hamed Tashakorian, Seyed Raheleh Ahmadian, Manouchehr Ashrafpour, Maryam Ghasemi-Kasman
Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model...
March 9, 2018: Neuroscience Letters
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Gunnar Poplawski, Tetsuhiro Ishikawa, Coralie Brifault, Corinne Lee-Kubli, Robert Regestam, Kenneth W Henry, Yasuhiro Shiga, HyoJun Kwon, Seiji Ohtori, Steven L Gonias, Wendy M Campana
Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes in the transcriptome of sensory neurons, which are instrumental for axon regeneration. The role of Schwann cells (SCs) in mediating these changes remains undefined. We tested the hypothesis that SCs regulate expression of genes in sensory neurons before and after PNS injury by comparing mice in which LDL Receptor-related Protein-1 (LRP1) is deleted in SCs (scLRP1-/- mice) with wild-type (scLRP1+/+ ) littermates...
March 9, 2018: Glia
Thomas V Wuttke, Foivos Markopoulos, Hari Padmanabhan, Aaron P Wheeler, Venkatesh N Murthy, Jeffrey D Macklis
Repair of complex CNS circuitry requires newly incorporated neurons to become appropriately, functionally integrated. One approach is to direct differentiation of endogenous progenitors in situ, or ex vivo followed by transplantation. Prior studies find that newly incorporated neurons can establish long-distance axon projections, form synapses and functionally integrate in evolutionarily old hypothalamic energy-balance circuitry. We now demonstrate that postnatal neocortical connectivity can be reconstituted with point-to-point precision, including cellular integration of specific, molecularly identified projection neuron subtypes into correct positions, combined with development of appropriate long-distance projections and synapses...
March 5, 2018: Nature Neuroscience
Tao Xiong, Yi Qu, Huiqin Wang, Hongju Chen, Jianghu Zhu, Fengyan Zhao, Rong Zou, Li Zhang, Dezhi Mu
Glycogen synthase kinase 3 beta (GSK-3β) plays an important role in neurological outcomes after brain injury. However, its roles and mechanisms in hypoxia-ischemia (HI) are unclear. Activation of mTOR complex 1 (mTORC1) has been proven to induce the synthesis of proteins associated with regeneration. We hypothesized that GSK-3β inhibition could activate the mTORC1 signaling pathway, which may reduce axonal injury and induce synaptic protein synthesis and functional recovery of synapses after HI. By analyzing a P7 rat model of cerebral HI and an in vitro ischemic (oxygen glucose deprivation) model, we found that GSK-3β inhibitors (GSK-3β siRNA or lithium chloride) activated mTORC1 signaling, leading to increased expression of synaptic proteins, including synapsin 1, PSD95, and GluR1, and the microtubule-associated protein Tau and decreased expression of the axonal injury-associated protein amyloid precursor protein...
February 28, 2018: Journal of Neuropathology and Experimental Neurology
Victor S C Wong, Cristina Picci, Michelle Swift, Max Levinson, Dianna Willis, Brett Langley
Damage to the CNS results in neuronal and axonal degeneration, and subsequent neurological dysfunction. Endogenous repair in the CNS is impeded by inhibitory chemical and physical barriers, such as chondroitin sulfate proteoglycans (CSPGs) and myelin-associated glycoprotein (MAG), which prevent axon regeneration. Previously, it has been demonstrated that the inhibition of axonal histone deacetylase-6 (HDAC6) can promote microtubule α-tubulin acetylation and restore the growth of CSPGs- and MAG-inhibited axons...
January 2018: ENeuro
Hongyi Liu, Yu Pu, Yaping Xu, He Xu, Huanhai Liu, Yin Cheng, Weihua Xu, Xiaoping Chen, Jingping Fan
The aim of this study was to investigate whether the transplantation of olfactory-ensheathing cells (OECs) could physiologically repair severely injured recurrent laryngeal nerve (RLN) in dogs. Adult Beagle dogs were surgically introduced with a 10-mm defect in the left RLN and transplanted with a nerve guide (NEUROLAC) containing dog olfactory mucosa-olfactory-ensheathing cells (OM-OECs) in matrigel. The effects of OM-OECs on the morphology, histology, and electrophysiology of the injured RLNs, glottis movement, and voice acoustics were comparatively studied...
February 28, 2018: Molecular and Cellular Biochemistry
Christina F Vogelaar, Shibajee Mandal, Steffen Lerch, Katharina Birkner, Jerome Birkenstock, Ulrike Bühler, Andrea Schnatz, Cedric S Raine, Stefan Bittner, Johannes Vogt, Jonathan Kipnis, Robert Nitsch, Frauke Zipp
Ongoing axonal degeneration is thought to underlie disability in chronic neuroinflammation, such as multiple sclerosis (MS), especially during its progressive phase. Upon inflammatory attack, axons undergo pathological swelling, which can be reversible. Because we had evidence for beneficial effects of T helper 2 lymphocytes in experimental neurotrauma and discovered interleukin-4 receptor (IL-4R) expressed on axons in MS lesions, we aimed at unraveling the effects of IL-4 on neuroinflammatory axon injury. We demonstrate that intrathecal IL-4 treatment during the chronic phase of several experimental autoimmune encephalomyelitis models reversed disease progression without affecting inflammation...
February 28, 2018: Science Translational Medicine
Geeta Shroff
Multiple sclerosis (MS), a complex disorder of the central nervous system (CNS), is characterized with axonal loss underlying long-term progressive disability. Currently available therapies for its management are able to slow down the progression but fail to treat it completely. Moreover, these therapies are associated with major CNS and cardiovascular adverse events, and prolonged use of these treatments may cause life-threatening diseases. Recent research has shown that cellular therapies hold a potential for CNS repair and may be able to provide protection from inflammatory damage caused after injury...
2018: Stem Cells and Cloning: Advances and Applications
Dan Liu, Daguo Mi, Tuanjie Zhang, Yanping Zhang, Junying Yan, Yaxian Wang, Xuefeng Tan, Ying Yuan, Yumin Yang, Xiaosong Gu, Wen Hu
The repair of peripheral nerve laceration injury to obtain optimal function recovery remains a big challenge in the clinic. Misdirection of regenerating axons to inappropriate target, as a result of forced mismatch of endoneurial sheaths in the case of end-to-end nerve anastomosis or nerve autografting, represents one major drawback that limits nerve function recovery. Here we tested whether tubulation repair of a nerve defect could be beneficial in terms of nerve regeneration accuracy and nerve function. We employed sequential retrograde neuronal tracing to assess the accuracy of motor axon regeneration into the tibial nerve after sciatic nerve laceration and entubulation in adult Sprague-Dawley rats...
February 21, 2018: Scientific Reports
Yun Zeng, Heng Han, Bing Tang, Jie Chen, Dan Mao, Min Xiong
BACKGROUND Spinal cord injury (SCI) causes a rapid loss of motor neurons, leading to weakness and paralysis. Transplantation of neural stem cells is known to restore the neuronal activity but is inefficient due to limited regenerative capability and low rate of survival. There has been an emphasis on the use of growth factors along with neural stem cells (NSCs) to enhance the neuronal recovery. Transplantation of recombinant NSCs with vascular endothelial growth factor (VEGF) might promote neuronal repair. This effect might be attributed to the reduced transient receptor potential vanilloid 1 (TRPV1) expression following transplantation...
February 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
C R Carvalho, S Wrobel, C Meyer, C Brandenberger, I F Cengiz, R López-Cebral, J Silva-Correia, G Ronchi, R L Reis, C Grothe, J M Oliveira, K Haastert-Talini
Peripheral nerve injuries (PNI) resulting in a gap to be bridged between the transected nerve ends are commonly reconstructed with autologous nerve tissue, but there is a need for valuable alternatives. This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels made from chitosan with a 5% degree of acetylation. The engineered constructs should remodel the structural support given to regenerating axons by the so-called bands of Büngner...
February 21, 2018: Biomaterials Science
Christine E Beattie, Stephen J Kolb
Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that result in reduced expression of the SMN protein. The SMN protein is an essential molecular chaperone that is required for the biogenesis of multiple ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs and to downstream RNA splicing alterations. SMN is also present in axons and dendrites and appears to have important roles in the formation of neuronal mRNA-protein complexes during development or neuronal repair...
February 17, 2018: Brain Research
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