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axon regeneration

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https://www.readbyqxmd.com/read/29053522/immediate-enhancement-of-nerve-function-using-a-novel-axonal-fusion-device-after-neurotmesis
#1
David Colton Riley, Richard B Boyer, Curt A Deister, Alonda C Pollins, Nancy L Cardwell, Nathaniel D Kelm, Mark D Does, Richard D Dortch, Ravinder Bamba, Robert Bruce Shack, Wesley P Thayer
BACKGROUND: The management of peripheral nerve injuries remains a large challenge for plastic surgeons. With the inability to fuse axonal endings, results after microsurgical nerve repair have been inconsistent. Our current nerve repair strategies rely upon the slow and lengthy process of axonal regeneration (~1 mm/d). Polyethylene glycol (PEG) has been investigated as a potential axonal fusion agent; however, the percentage of axonal fusion has been inconsistent. The purpose of this study was to identify a PEG delivery device to standardize outcomes after attempted axonal fusion with PEG...
October 19, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29053076/protective-effect-of-biodegradable-nerve-conduit-against-peripheral-nerve-adhesion-after-neurolysis
#2
Kosuke Shintani, Takuya Uemura, Kiyohito Takamatsu, Takuya Yokoi, Ema Onode, Mitsuhiro Okada, Hiroaki Nakamura
OBJECTIVE Peripheral nerve adhesion caused by extraneural and intraneural scar formation after neurolysis leads to nerve dysfunction. The authors previously developed a novel very flexible biodegradable nerve conduit composed of poly(L-lactide) and poly(ε-caprolactone) for use in peripheral nerve regeneration. In the present study, they investigated the effect of protective nerve wrapping on preventing adhesion in a rat sciatic nerve adhesion model. METHODS Rat sciatic nerves were randomly assigned to one of the following four groups: a no-adhesion group, which involved neurolysis alone without an adhesion procedure; an adhesion group, in which the adhesion procedure was performed after neurolysis, but no treatment was subsequently administered; a nerve wrap group, in which the adhesion procedure was performed after neurolysis and protective nerve wrapping was then performed with the nerve conduit; and a hyaluronic acid (HA) group, in which the adhesion procedure was performed after neurolysis and nerve wrapping was then performed with a 1% sodium HA viscous solution...
October 20, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29051003/spontaneous-regeneration-of-nerve-fiber-and-irreversibility-of-corporal-smooth-muscle-fibrosis-after-cavernous-nerve-crush-injury-evidence-from-serial-transmission-electron-microscopy-and-intracavernous-pressure
#3
Yi-No Wu, Kuo-Chiang Chen, Chun-Hou Liao, Han-Sun Chiang
OBJECTIVES: To determine the pathophysiological progresses following bilateral cavernous nerve crushing (BCNC) injury, as an index for a treatment point and establishment of adequate treatment strategies for neurogenic erectile dysfunction (ED). METHODS: Thirty-six rats were assigned to 1 of 6 groups, and BCNC or sham surgery was performed. Functional testing and ultrastructural analyses were performed immediately and at 7, 14, 21, and 28 d after the cavernous nerve (CN) injury (n = 6)...
October 16, 2017: Urology
https://www.readbyqxmd.com/read/29045878/homodimeric-kinesin-2-kif3cc-promotes-microtubule-dynamics
#4
Stephanie Guzik-Lendrum, Ivan Rayment, Susan P Gilbert
KIF3C is one subunit of the functional microtubule-based kinesin-2 KIF3AC motor, an anterograde cargo transporter in neurons. However, KIF3C has also been implicated as an injury-specific kinesin that is a key regulator of axonal growth and regeneration by promoting microtubule dynamics for reorganization at the neuronal growth cone. To test its potential role as a modulator of microtubule dynamics in vitro, an engineered homodimeric KIF3CC was incorporated into a dynamic microtubule assay and examined by total internal reflection fluorescence microscopy...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29044892/mouse-parthenogenetic-embryonic-stem-cells-with-biparental-like-expression-of-imprinted-genes-generate-cortical-like-neurons-that-integrate-into-the-injured-adult-cerebral-cortex
#5
Annie Varrault, Sigrid Eckardt, Benoît Girard, Anne Le Digarcher, Isabelle Sassetti, Céline Meusnier, Chantal Ripoll, Armen Badalyan, Federica Bertaso, K John McLaughlin, Laurent Journot, Tristan Bouschet
One strategy for stem cell-based therapy of the cerebral cortex involves the generation and transplantation of functional, histocompatible cortical-like neurons from embryonic stem cells (ESCs). Diploid parthenogenetic Pg-ESCs have recently emerged as a promising source of histocompatible ESC derivatives for organ regeneration but their utility for cerebral cortex therapy is unknown. A major concern with Pg-ESCs is genomic imprinting. In contrast with biparental Bp-ESCs derived from fertilized oocytes, Pg-ESCs harbor two maternal genomes but no sperm-derived genome...
October 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/29044770/effects-of-forced-passive-and-voluntary-exercise-on-spinal-motoneurons-changes-after-peripheral-nerve-injury
#6
Ariadna Arbat-Plana, Xavier Navarro, Esther Udina
After peripheral nerve injury, there are important changes at the spinal level that can lead to disorganization of the central circuitry and thus, compromise functional recovery even if axons are able to successfully regenerate and reinnervate their target organs. Physical rehabilitation is a promising strategy to modulate these plastic changes and thus, to improve functional recovery after damage of the nervous system. Forced exercise in a treadmill is able to partially reverse the synaptic stripping and the loss of perineuronal nets that motoneurons suffer after peripheral nerve injury in animal models...
October 17, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29044129/priming-with-fgf2-stimulates-human-dental-pulp-cells-to-promote-axonal-regeneration-and-locomotor-function-recovery-after-spinal-cord-injury
#7
Kosuke Nagashima, Takahiro Miwa, Hitomi Soumiya, Daisuke Ushiro, Tomoko Takeda-Kawaguchi, Naritaka Tamaoki, Saho Ishiguro, Yumi Sato, Kei Miyamoto, Takatoshi Ohno, Masatake Osawa, Takahiro Kunisada, Toshiyuki Shibata, Ken-Ichi Tezuka, Shoei Furukawa, Hidefumi Fukumitsu
Human dental pulp cells (DPCs), adherent cells derived from dental pulp tissues, are potential tools for cell transplantation therapy. However, little work has been done to optimize such transplantation. In this study, DPCs were treated with fibroblast growth factor-2 (FGF2) for 5-6 consecutive serial passages and were transplanted into the injury site immediately after complete transection of the rat spinal cord. FGF2 priming facilitated the DPCs to promote axonal regeneration and to improve locomotor function in the rat with spinal cord injury (SCI)...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29044090/contralateral-eye-surgery-with-adjustable-suture-for-management-of-third-nerve-palsy-with-aberrant-regeneration
#8
Phuong Thi Thanh Nguyen, Shailja Tibrewal, Suma Ganesh
Aberrant regeneration of the third nerve following its palsy is commonly seen after trauma and compressive lesions. This phenomenon is thought to result due to misdirection of the regenerating axons. Surgical management is a great challenge in the third nerve palsy owing to multiple muscle involvement and is often accompanied by ptosis and poor Bell's phenomenon. We present a case of a 27-year-old male who developed isolated complete third nerve palsy of the left eye following head trauma. Features of aberrant regeneration were seen after 6 months, namely, inverse Duane's sign and Pseudo-Von Graefe's sign...
October 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29038581/transcriptional-repression-of-plxnc1-by-lmx1a-and-lmx1b-directs-topographic-dopaminergic-circuit-formation
#9
Audrey Chabrat, Guillaume Brisson, Hélène Doucet-Beaupré, Charleen Salesse, Marcos Schaan Profes, Axelle Dovonou, Cléophace Akitegetse, Julien Charest, Suzanne Lemstra, Daniel Côté, R Jeroen Pasterkamp, Monica I Abrudan, Emmanouil Metzakopian, Siew-Lan Ang, Martin Lévesque
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29033188/ppp1cc-is-associated-with-astrocyte-and-microglia-proliferation-after-traumatic-spinal-cord-injury-in-rats
#10
Xiaojuan Liu, Shen Huang, Chun Liu, Xia Liu, Yuntian Shen, Zhiming Cui
Reactive astrogliosis and microgliosis after spinal cord injury (SCI) contribute to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte and microglia proliferation upon injury remain partially understood. Protein phosphatase 1, catalytic subunit, gamma isozyme (PPP1CC) participates in cell proliferation, differentiation and apoptosis. However, the expression and functions of PPP1CC following SCI are still unknown. In this study, an acute spinal cord contusion injury model in adult rats was established to investigate the potential role of PPP1CC during the pathological process of SCI...
September 28, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29030922/the-role-of-mitochondria-in-axon-development-and-regeneration
#11
REVIEW
George M Smith, Gianluca Gallo
Mitochondria are dynamic organelles that undergo transport, fission and fusion. The three main functions of mitochondria are to generate ATP, buffer cytosolic calcium and generate reactive oxygen species. A large body of evidence indicates that mitochondria are either primary targets for neurological disease states and nervous system injury, or are major contributors to the ensuing pathologies. However, the roles of mitochondria in the development and regeneration of axons have just begun to be elucidated. Advances in the understanding of the functional roles of mitochondria in neurons had been largely impeded by insufficient knowledge regarding the molecular mechanisms that regulate mitochondrial transport, stalling, fission/fusion and a paucity of approaches to image and analyze mitochondria in living axons at the level of the single mitochondrion...
October 14, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29030051/determinants-of-axon-growth-plasticity-and-regeneration-in-the-context-of-spinal-cord-injury
#12
REVIEW
Angela R Filous, Jan M Schwab
The mechanisms that underlie recovery after injury of the central nervous system have rarely been definitively established. Axon re-growth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery. The attributed functional relevance of axon regrowth however will depend on a number of subsequent conditional neurobiological modifications, including myelination and synapse formation but also pruning of aberrant connectivity. Despite the ability to revamp axon outgrowth by altering an increasing number of extracellular and intracellular targets, disentangling which axons are responsible for the recovery of function from those that are functionally silent, or even contributing to aberrant functions, remains a crucial link between enhancing axonal growth profiles to functional improvement...
October 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29024435/efect-of-longitudinally-oriented-collagen-conduit-combined-with-nerve-growth-factor-on-nerve-regeneration-after-dog-sciatic-nerve-injury
#13
Yao Yao, Yi Cui, Yannan Zhao, Zhifeng Xiao, Xing Li, Sufang Han, Bing Chen, Yongxiang Fang, Piao Wang, Juli Pan, Jianwu Dai
The research on artificial nerve conduits has become a focus of study in peripheral nerve reconstruction so as a possible replacement for the treatment of autologous nerve grafts in clinics. In this study, we used longitudinally oriented collagen conduit (LOCC) combined with nerve growth factor (NGF) to reconstruct long distance of sciatic nerve defects (35 mm) in adult dog model. The long term follow-up evaluation demonstrated that the LOCC/NGF conduit allowed functional and morphological nerve regeneration at the transection site of the injured sciatic nerve...
October 10, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/29018286/complement-protein-c3-suppresses-axon-growth-and-promotes-neuron-loss
#14
Sheri L Peterson, Hal X Nguyen, Oscar A Mendez, Aileen J Anderson
The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3(-/-) mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3(+/+) mice...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993995/pi3k-akt-and-erk-mapk-signaling-promote-different-aspects-of-neuron-survival-and-axonal-regrowth-following-rat-facial-nerve-axotomy
#15
Haitao Huang, Huawei Liu, Rongzeng Yan, Min Hu
The ERK/MAPK and PI3K/Akt signaling pathways play important role in neuronal survival and axonal regeneration after peripheral nerve injury. However, the relative importance and degree of functional overlap of the two pathways are still debated due to lack of in-vivo data. We used rats which underwent a facial nerve axotomy, and examined subsequent ERK/MAPK and PI3K/Akt signaling activity by quantifying phosphorylation of ERK and Akt. We also assessed the survival rate of facial neurons, number of regenerated axons, and the length of axonal regrowth in axotomized animals treated with an inhibitor of ERK/MAPK (U0126) or PI3K/Akt (LY294002) phosphorylation, or with vehicle...
October 9, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28993483/the-ste20-family-kinases-map4k4-mink1-and-tnik-converge-to-regulate-stress-induced-jnk-signaling-in-neurons
#16
Martin Larhammar, Sarah Huntwork-Rodriguez, York Rudhard, Arundhati Sengupta-Ghosh, Joseph W Lewcock
The c-Jun-N-terminal Kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration following acute injury or in chronic neurodegenerative disease. Dual Leucine Zipper Kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, TNIK, and MINK1 as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, TNIK, and MINK1 act redundantly to regulate DLK activation and downstream JNK dependent phosphorylation of c-Jun in response to stress...
October 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28993312/mmp-14-overexpression-correlates-with-the-neurodegenerative-process-in-familial-amyloidotic-polyneuropathy
#17
Diana Martins, João Moreira, Nádia Pereira Gonçalves, Maria João Saraiva
Levels of matrix metalloproteases (MMPs) can be differentially regulated in response to injury or neurological diseases. For instance, it is known that selective and short-term inhibition of MMP-14, a membrane-type 1 MMP, accelerates axon regeneration. Because axon growth and regeneration is impaired in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by misfolding and deposition of mutant transthyretin (TTR) in the peripheral nervous system (PNS), we presently investigated the expression levels and the potential role for MMP-14 in this condition...
October 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28990762/multichanneled-nerve-guidance-conduit-with-spatial-gradients-of-neurotrophic-factors-and-oriented-nanotopography-for-repairing-the-peripheral-nervous-system
#18
Yo-Cheng Chang, Ming-Hong Chen, Shih-Yung Liao, Hsi-Chin Wu, Chen-Hsiang Kuan, Jui-Sheng Sun, Tzu-Wei Wang
Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth...
October 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28987564/roles-of-csgalnact1-a-key-enzyme-in-regulation-of-cs-synthesis-in-neuronal-regeneration-and-plasticity
#19
REVIEW
Michihiro Igarashi, Kosei Takeuchi, Sayaka Sugiyama
Chondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth. Most previous studies used a bacterial CS-degrading enzyme to investigate the physiological roles of CS...
October 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28986946/effect-of-decellularized-spinal-scaffolds-on-spinal-axon-regeneration-in-rats
#20
Junyi Zhu, Yingfeng Lu, Fangzheng Yu, Lebin Zhou, Jiawei Shi, Qihui Chen, Weili Ding, Xin Wen, Yu-Qiang Ding, Jin Mei, Jian Wang
A series of complex influencing factors lead to failure of neural regeneration after spinal cord injury (SCI). Up to now, there is no robust treatment that can restore the loss of function caused by injury. Because damaged spinal axons do not spontaneously regenerate in their naturally inhibitory microenvironments, biomaterials that induce neural regeneration to appear as attractive treatments to improve the microenvironmental conditions after SCI. In this study, we report the novel use of decellularized (DC) scaffolds to provide contact guidance for axonal regrowth in vivo...
October 7, 2017: Journal of Biomedical Materials Research. Part A
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