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Axonal injury

Ashkan Afshari, Lyly Nguyen, Nathaniel D Kelm, Justine S Kim, Nancy L Cardwell, Alonda C Pollins, Ravinder Bamba, R Bruce Shack, Mark D Does, Wesley P Thayer
PURPOSE: Given no definite consensus on the accepted autograft orientation during peripheral nerve injury repair, we compare outcomes between reverse and normally oriented autografts using an advanced magnetic resonance imaging technique, diffusion tensor imaging. METHODS: Thirty-six female Sprague-Dawley rats were divided into 3 groups: sham-left sciatic nerve isolation without injury, reverse autograft-10-mm cut left sciatic nerve segment reoriented 180° and used to coapt the proximal and distal stumps, or normally oriented autograft-10-mm cut nerve segment kept in its normal orientation for coaptation...
February 13, 2018: Annals of Plastic Surgery
Edyta Olakowska, Wiesław Marcol, Adam Właszczuk, Izabella Woszczycka-Korczyńska, Joanna Lewin-Kowalik
BACKGROUND: Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma. OBJECTIVES: The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
He-Lin Xu, Fu-Rong Tian, Jian Xiao, Pian-Pian Chen, Jie Xu, Zi-Liang Fan, Jing-Jing Yang, Cui-Tao Lu, Ying-Zheng Zhao
Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI). Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP), as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM) as an affinity depot of drug...
2018: International Journal of Nanomedicine
Sonja Mertsch, Katrin Schlicht, Harutyun Melkonyan, Stefan Schlatt, Solon Thanos
BACKGROUND: Retinal ganglion cells (RGCs) of mammals lose the ability to regenerate injured axons during postnatal maturation, but little is known about the underlying molecular mechanisms. OBJECTIVE: It remains of particular importance to understand the mechanisms of axonal regeneration to develop new therapeutic approaches for nerve injuries. METHODS: Retinas from newborn to adult monkeys (Callithrix jacchus)1 were obtained immediately after death and cultured in vitro...
2018: Restorative Neurology and Neuroscience
Yosuke Ohtake, Koji Matsuhisa, Masayuki Kaneko, Soshi Kanemoto, Rie Asada, Kazunori Imaizumi, Atsushi Saito
Adult mammalian peripheral neurons have an intrinsic regrowth capacity in response to axonal injury. The induction of calcium ion (Ca 2+ ) oscillations at an injured site is critical for the regulation of regenerative responses. In polarized neurons, distal axonal segments contain a well-developed endoplasmic reticulum (ER) network that is responsible for Ca 2+ homeostasis. Although these characteristics implicate the relevance among injury-induced Ca 2+ dynamics, axonal ER-derived signaling, and regenerative responses propagated along the axons, the details are not fully understood...
February 10, 2018: Neuroscience
Ethan I Meltzer, Fiona E Costello, Elliot M Frohman, Teresa C Frohman
BACKGROUND: Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments...
March 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Arnau Hervera, Francesco De Virgiliis, Ilaria Palmisano, Luming Zhou, Elena Tantardini, Guiping Kong, Thomas Hutson, Matt C Danzi, Rotem Ben-Tov Perry, Celio X C Santos, Alexander N Kapustin, Roland A Fleck, José Antonio Del Río, Thomas Carroll, Vance Lemmon, John L Bixby, Ajay M Shah, Mike Fainzilber, Simone Di Giovanni
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis...
February 12, 2018: Nature Cell Biology
Esther Barreiro
Skeletal muscle weakness is common in the intensive care units (ICU). Approximately 50% of patients under mechanical ventilation for more than 7 days show signs of ICU-acquired muscle weakness. In these patients, muscle weakness may be the result of axonal polyneuropathy, myopathy or a combination of both. The commonest risk factors in patients with ICU-acquired weakness (AW) are the severity and duration of the systemic inflammatory response, duration of the stay in the ICU and of mechanical ventilation, hyperglycemia, hypoalbuminemia, parenteral nutrition, and administration of corticosteroids and of neuromuscular blocking agents...
January 2018: Annals of Translational Medicine
Yurie Yamada, Atsushi Ohazama, Takeyasu Maeda, Kenji Seo
Activation of Shh signaling is known to be observed following injury of the peripheral nerves such as the sciatic nerve. However, the precise role of Shh signaling during peripheral nerve regeneration is not fully understood. The inferior alveolar nerve (IAN) is most commonly injured during oral surgery. Unlike the sciatic nerve, the IAN is isolated from other craniofacial tissues, as it resides in a long bony canal within the mandible. The IAN is thus an excellent experimental model for investigating peripheral nerve regeneration...
February 8, 2018: Neuroscience Letters
David Oliveira Dias, Christian Göritz
Following lesions to the central nervous system, scar tissue forms at the lesion site. Injury often severs axons and scar tissue is thought to block axonal regeneration, resulting in permanent functional deficits. While scar-forming astrocytes have been extensively studied, much less attention has been given to the fibrotic, non-glial component of the scar. We here review recent progress in understanding fibrotic scar formation following different lesions to the brain and spinal cord. We specifically highlight recent evidence for pericyte-derived fibrotic scar tissue formation, discussing the origin, recruitment, function and therapeutic relevance of fibrotic scarring...
February 8, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Xiaoyun Xu, Bethany Bass, William M McKillop, Janina Mailloux, Tony Liu, Nicole M Geremia, Todd Hryciw, Arthur Brown
The partial recovery that can occur after a stroke has been attributed to structural and functional plasticity that compensate for damage and lost functions. This plasticity is thought to be limited in part by the presence of growth inhibitors in the central nervous system. Blocking or reducing signals from inhibitors of axonal sprouting such as Nogo and chondroitin sulfate proteoglycans (CSPGs) increases post-stroke axonal sprouting and improves recovery. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and demonstrated that conditional Sox9 ablation leads to increased axonal sprouting and improved recovery after spinal cord injury...
February 6, 2018: Experimental Neurology
Wissam Chiha, Chrisna J LeVaillant, Carole A Bartlett, Alex W Hewitt, Phillip E Melton, Melinda Fitzgerald, Alan R Harvey
BACKGROUND: Partial transection (PT) of the optic nerve is an established experimental model of secondary degeneration in the central nervous system. After a dorsal transection, retinal ganglion cells (RGCs) with axons in ventral optic nerve are intact but vulnerable to secondary degeneration, whereas RGCs in dorsal retina with dorsal axons are affected by primary and secondary injuries. Using microarray, we quantified gene expression changes in dorsal and ventral retina at 1 and 7 days post PT, to characterize pathogenic pathways linked to primary and secondary degeneration...
2018: PloS One
Anne Bolleboom, Godard C W de Ruiter, J Henk Coert, Bastiaan Tuk, Jan C Holstege, Johan W van Neck
OBJECTIVE Traumatic neuromas may develop after nerve injury at the proximal nerve stump, which can lead to neuropathic pain. These neuromas are often resistant to therapy, and excision of the neuroma frequently leads to recurrence. In this study, the authors present a novel surgical strategy to prevent neuroma formation based on the principle of centro-central anastomosis (CCA), but rather than directly connecting the nerve ends to an autograft, they created a loop using a 3D-printed polyethylene Y-shaped conduit with an autograft in the distal outlets...
February 9, 2018: Journal of Neurosurgery
Matthew R MacEwan, Paul Gamble, Manu Stephen, Wilson Z Ray
OBJECTIVE Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery...
February 9, 2018: Journal of Neurosurgery
Linda S Sorkin, Kelly A Eddinger, Sarah A Woller, Tony L Yaksh
Neurogenic inflammation results from the release of biologically active agents from the peripheral primary afferent terminal. This release reflects the presence of releasable pools of active product and depolarization-exocytotic coupling mechanisms in the distal afferent terminal and serves to alter the physiologic function of innervated organ systems ranging from the skin and meninges to muscle, bone, and viscera. Aside from direct stimulation, this biologically important release from the peripheral afferent terminal can be initiated by antidromic activity arising from five anatomically distinct points of origin: (i) afferent collaterals at the peripheral-target organ level, (ii) afferent collaterals arising proximal to the target organ, (iii) from mid-axon where afferents lacking myelin sheaths (C fibers and others following demyelinating injuries) may display crosstalk and respond to local irritation, (iv) the dorsal root ganglion itself, and (v) the central terminals of the afferent in the dorsal horn where local circuits and bulbospinal projections can initiate the so-called dorsal root reflexes, i...
February 8, 2018: Seminars in Immunopathology
Yaxian Wang, Qianqian Shan, Jiacheng Pan, Sheng Yi
Actin cytoskeleton regulates many essential biological functions, including cellular development, shape, polarity, and motility. The organization of actin cytoskeleton has also been associated with numerous physiological and pathological conditions, for instance, the elongation of axonal growth cone during peripheral nerve regeneration. However, the spatio-temporal expression patterns of actin cytoskeleton-related genes and the specific roles of actin cytoskeleton following peripheral nerve injury have not been fully revealed...
2018: Frontiers in Physiology
Kwok M Ho, Steve Honeybul, Ravi Ambati
BACKGROUND: Diffuse axonal injury (DAI) detected on magnetic resonance imaging (MRI) may be useful to predict outcome after traumatic brain injury (TBI). METHODS: This study compared the ability of the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) prognostic model with DAI on MRI, to predict 18-months neurological outcome in 56 patients who had required a decompressive craniectomy after TBI. RESULTS: Of the 56 patients included in the study (19 scans occurred within 14 days; median time for all patients 24 days, interquartile range 14-42), 18 (32%) had evidence of DAI on the MRI scans...
February 5, 2018: World Neurosurgery
Cláudio Gouveia Roque, Ulrich Hengst
While PIWI-interacting RNAs (piRNAs) are primarily recognized as guardians of genome integrity, new functions of these small non-coding RNAs are emerging. In this issue, Kim et al. (2018) describe a piRNA-based mechanism that limits axon regeneration in C. elegans.
February 7, 2018: Neuron
Carolin Ruven, Smaranda-Ruxandra Badea, Wai-Man Wong, Wutian Wu
When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation...
February 6, 2018: Journal of Neuropathology and Experimental Neurology
Hozo Matsuoka, Hiroyuki Tanaka, Junichi Sayanagi, Toru Iwahashi, Koji Suzuki, Shunsuke Nishimoto, Kiyoshi Okada, Tsuyoshi Murase, Hideki Yoshikawa
Neurotropin® (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study was to investigate the effects of NTP on Schwann cells (SCs) in vitro and in vivo, which play an important role in peripheral nerve regeneration. In SCs, NTP upregulated protein kinase B (AKT) activity and Krox20 and downregulated extracellular signal-regulated kinase1/2 activity under both growth and differentiation conditions, enhanced the expression of myelin basic protein and protein zero under the differentiation condition...
February 8, 2018: International Journal of Molecular Sciences
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