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Axonal regeneration

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https://www.readbyqxmd.com/read/29033188/ppp1cc-is-associated-with-astrocyte-and-microglia-proliferation-after-traumatic-spinal-cord-injury-in-rats
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28986688/unconventional-myosin-id-is-involved-in-remyelination-after-cuprizone-induced-demyelination
#12
Reiji Yamazaki, Hiroko Baba, Yoshihide Yamaguchi
Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes (OLs), which wrap their plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we reported that myosin ID (Myo1d) is distributed in rat CNS myelin and is especially enriched in the outer and inner cytoplasm-containing loops...
October 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28982707/post-injury-induction-of-activated-erbb2-selectively-hyperactivates-denervated-schwann-cells-and-promotes-robust-dorsal-root-axon-regeneration
#13
Seung Baek Han, Hyukmin Kim, Hyunkyoung Lee, Matthew Grove, George M Smith, Young-Jin Son
Following nerve injury, denervated Schwann cells (SCs) convert to repair SCs, which enable regeneration of peripheral axons. However, the repair capacity of SCs and the regenerative capacity of peripheral axons are limited. In the present studies we examined a potential therapeutic strategy to enhance the repair capacity of SCs, and tested its efficacy in enhancing regeneration of dorsal root (DR) axons, whose regenerative capacity is particularly weak. We used male and female mice of a doxycycline-inducible transgenic line to induce expression of constitutively active ErbB2 (caErbB2) selectively in SCs after DR crush or transection...
October 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28981095/rtn1-c-mediates-cerebral-ischemia-reperfusion-injury-via-er-stress-and-mitochondria-associated-apoptosis-pathways
#14
Lingli Gong, Yuewen Tang, Ran An, Muya Lin, Lijian Chen, Jian Du
The reticulon family has been found to induce apoptosis, inhibit axon regeneration and regulate protein trafficking. However, little is known about the mechanisms of how reticulon proteins are involved in neuronal death-promoting processes during ischemia. Here, we report that the expression of Reticulon Protein 1-C (RTN1-C) was associated with the progression of cerebral ischemia/reperfusion (I/R) injury. Using a combination of rat middle cerebral artery occlusion (MCAO) stroke and oxygen-glucose deprivation followed by reoxygenation (OGD/R) models, we determined that the expression of RTN1-C was significantly increased during cerebral ischemic/reperfusion...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28977718/sustained-cell-body-reactivity-and-loss-of-neun-in-a-subset-of-axotomized-bulbospinal-neurons-after-a-chronic-high-cervical-spinal-cord-injury
#15
Fannie Darlot, Stéphane Vinit, Valéry Matarazzo, Anne Kastner
Following central nervous system lesion, the ability of injured axons to regrowth may depend on the level and duration of the injured cell body response (CBR). Therefore, in order to investigate whether axotomized brainstem neurons maintain a durable growth-competent state after spinal cord injury, we studied the effect of a chronic C2 hemisection in rats on the expression of various CBR markers involved in axon regeneration, such as c-Jun, ATF-3, HSP27, NO synthase (NOS), and also of the neural mature phenotype marker NeuN, in the bulbospinal respiratory neurons as compared to the Gigantocellularis nucleus...
October 4, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28975768/a-physicochemically-optimized-and-neuroconductive-biphasic-nerve-guidance-conduit-for-peripheral-nerve-repair
#16
Alan J Ryan, William A Lackington, Alan J Hibbitts, Austyn Matheson, Tijna Alekseeva, Anna Stejskalova, Phoebe Roche, Fergal J O'Brien
Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates...
October 4, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28974767/the-neurotrophic-effects-of-different-human-dental-mesenchymal-stem-cells
#17
Mallappa K Kolar, Vinay N Itte, Paul J Kingham, Lev N Novikov, Mikael Wiberg, Peyman Kelk
The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974639/can-injured-adult-cns-axons-regenerate-by-recapitulating-development
#18
REVIEW
Brett J Hilton, Frank Bradke
In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS...
October 1, 2017: Development
https://www.readbyqxmd.com/read/28973496/single-local-application-of-tgf-%C3%AE-promotes-a-proregenerative-state-throughout-a-chronically-injured-nerve
#19
Wale Sulaiman, Thomas Dreesen, Doan Nguyen
BACKGROUND: The lack of nerve regeneration and functional recovery occurs frequently when injuries involve large nerve trunks because insufficient mature axons reach their targets in the distal stump and because of the loss of neurotrophic support, primarily from Schwann cells (SCs). OBJECTIVE: To investigate whether a single application of transforming growth factor-beta (TGF-β) plus forskolin or forskolin alone can promote and support axonal regeneration through the distal nerve stump...
July 21, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28972819/schwann-cell-phenotype-changes-in-aging-human-dental-pulp
#20
E Couve, M Lovera, K Suzuki, O Schmachtenberg
Schwann cells are glial cells that support axonal development, maintenance, defense, and regeneration in the peripheral nervous system. There is limited knowledge regarding the organization, plasticity, and aging of Schwann cells within the dental pulp in adult permanent teeth. The present study sought to relate changes in the pattern of Schwann cell phenotypes between young and old adult teeth with neuronal, immune, and vascular components of the dental pulp. Schwann cells are shown to form a prominent glial network at the dentin-pulp interface, consisting of nonmyelinating and myelinating phenotypes, forming a multicellular neuroimmune interface in association with nerve fibers and dendritic cells...
October 1, 2017: Journal of Dental Research
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