Paravertebral turnover flaps for closure of large spinal defects following tethered cord repair. Photochemistry and photobiology of light absorption by living cells. Photoengineering of neural tissue repair processes in peripheral nerves and the spinal cord: Surgical anatomy of the cervical segment of the hypoglossal nerve.
Clinical anatomy New York, N. Phototherapy for enhancing peripheral nerve repair: Report of a case. Sackler Faculty of Medicine. This site Global search. The versatility of this technique gives room for further scaffold improvements, such as tuning the mechanical properties of the tubular structure or providing biomimetic functionalization. Moreover, these guidance conduits can be loaded with various fillers, including collagen, fibrin or self-assembling peptide gels or loaded with neurotrophic factors and seeded with cells.
Electrospun scaffolds can also be synthesized in different micro-architectures to regenerate lesions in other tissues such as skin and bone. Based on tissue-engineering technology, Rochkind et al. The bioscaffold served as a regenerative environment for repair. An option for nerve gaps beyond 3 cm could be the cold-preserved allografts seeded with autologous SCs.
Based on the physiology of nerve recovery after an injury, Kosins et al. An epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination, but was followed by a faster and improved SC remyelination compared with the control group. The regenerated axons partially derived from the proximal motor axons. The delivery of factors to the site of injury and their dosage regimen have been major problems in this field of research.
Neuroprotective therapy is aimed at boosting the beneficial autoimmune response to injury-associated self-antigens. Immune cells play a role in the regulation of motor neuron survival after a peripheral nerve injury, and the antigen glatiramer acetate is known to affect T-cell immunity on peripheral nerve regeneration. Related to the inflammatory response, the cyclooxygenase-2 COX-2 is strongly upregulated around the nerve injury site.
After an experimental study in rats, the anti-inflammatory drug celecoxib is suggested to be considered in the treatment of PNI. Considering that cholesterol and lipids are needed for reconstructing myelin sheaths and axon extension, Li et al. The postinjury treatment with apoE-mimetic peptide promoted axonal regrowth after 2 weeks of treatment compared with the control group. The morphometric analysis showed an increased thickness of myelin sheaths, an increased clearance of myelin debris and the markers of axon regeneration and remyelination.
Erythropoietin may have neuroprotective, and perhaps have neurotrophic roles 89 , 90 in acute sciatic nerve crush injury.
This protective effect could have clinical relevance, especially since it was detectable even when erythropoietin had been administered up to 1 week after injury. Many experiments have been undertaken using different factors to facilitate better or faster nerve stump growth: Another organic molecule implicated in nervous system development and repair is the alpha 2.
The application of functional polysialic acid considerably improved the remyelination of regenerated axons distal to the injury site, indicating that effects on SCs in the denervated nerve may underlie the functional effects seen in motor recovery. Valproic acid 95 enhanced recovery by promoting neurite outgrowth, activating kinase pathway and increasing growth cone in neuroblastoma cells.
Acetyl- l -carnitine prevented neuronal loss by increasing their aerobic capacity. Vitamin D2 stimulated axon regeneration when added to a nerve autograft in rats. Glycine is an inhibitory neurotransmitter in the brain stem and spinal cord, and it also plays a critical role as a modulator of NMDA receptors. In traditional Chinese medicine, Lumbricus has been used to promote nerve function for hundreds of years, based on the idea that earthworms regenerated amputated parts of their body if the nervous system was intact.
In rats, the aqueous extract of Radix Hedysari Prescription is beneficial, suggesting the potential clinical application of Hedysari polysaccharides for the treatment of peripheral nerve injury in humans. The oral intake of the Japanese natto fermented soybean had the potential to augment regeneration in peripheral nerve injury, given its similar biological activity to tissue-type plasminogen activator t-PA that mediated by the clearance of fibrin and decreased production of TNF-alpha.
Other animal studies focus on the role of transcription factors, such as Sox11, in the functional and anatomical recovery after a PNI. Although most studies are based on products that hypothetically enhance the process of reinervation, there are fewer that did not show any satisfactory results. Diethyldithiocarbamate is known for its multiplicity of action that exerts both pro- and antioxidant effects. In PNI, the exposure to diethyldithiocarbamate adversely affected recovery.
To bridge the nerve defects, a chitosan-collagen film has also been used. Low-power laser irradiation laser phototherapy alters nerve cell activity, inducing upregulation of several neurotrophic growth factors and extracellular matrix proteins, which support neurite outgrowth. By altering the intensity or temporal pattern of injury-induced CGRP expression, phototherapy could optimize the rate of regeneration and target innervations and neuronal survival of axotomized neurons. In cell cultures, laser irradiation accelerates migration, nerve cell growth and fiber sprouting Rochkind et al.
In denervated muscles, animal studies suggest Rochkind et al. The function of denervated muscles could be restored to a very substantial degree by laser treatment initiated at the earliest possible stage postinjury. In peripheral nerve injury, laser phototherapy has shown an immediate protective effect.
It maintains functional activity of the injured nerve for a long period, decreases scar tissue formation at the injury site, decreases degeneration in corresponding motor neurons of the spinal cord and significantly increases axonal growth and myelinization. They carried out a randomized controlled trial in patients who had experienced substantial axonal loss in the median nerve from severe compression in the carpal tunnel.
They demonstrated that effects similar to those observed in animal studies could also be attained in humans. Acupunture has been a traditional Chinese practice of stimulating nerve regeneration. Fifty-four patients were treated by electric acupuncture and compared with 54 controls who received supportive medication.
The changes after treatment were observed chiefly by electromyography, while sensory and motor improvements were also recorded as auxiliary indicators. Acupunture was effective in 50 patients The patients in the acupuncture group were significantly better than those in the control group; nerve injuries should be treated as early as possible; the radial nerve and the common peroneal nerve recovered faster than others; cases not surgically explored recovered faster than those that were, and patients with prompt propagation of the needling sensation recovered significantly faster than those with slow propagation.
The relationship of proprioceptive kinesthetic feedback to motor physiology lead Brudny et al. EMG feedback induced significant functional recovery. However, we did not include this study given the heterogeneous group over all feedback therapy. The strategies for nerve regeneration include a variety of surgical procedures, grafting, new biologically based technologies and tissue engineering. In the management of nerve injuries, most of the published studies focus on bridging methods and nerve conduits.
Research has focused on conservative therapies to enhance nerve regeneration. Few studies have been performed 59 , 69 , 14 , in humans. All experiments with physical therapy modalities, and their effectiveness are not proved. Laser phototherapy has been studied in relative depth, but the studies involve small cohorts of patients, different nerves and etiology of injury. Most experiments are performed in animal models. Physical therapies, growth factors, cell sources and some proteins intervene at the lesion site, since the location is usually promptly available at the time of nerve repair.
An advantage of animal models is the opportunity to perform controlled experiments, but the therapies used in each study have been only compared with a control group and not against each other. It is difficult to measure superiority given the lack of a standard design: Although each of the hypotheses is proved in animals, translation to clinical practice in humans is missing. In vitro investigations concentrate on genetically modified cell sources 35 , 39 , 40 and neurotrophic factors 42 , 43 , 46 to bridge extensive nerve defects.
They also study the endogenous response to nerve injury 47 , 37 and the mechanisms of cell differentiation to provide a more accessible source of nerve cells, 38 and molecular targets to enhance axonal regeneration. However, their evidence is still poor, their results are not reliable and their clinical application is limited. Other reviews on PNI management are mostly based on experiments in animals, or in vitro and usually focus on specific areas of research: Many modalities have been proposed to promote nerve healing and restore function.
Despite this, essentially none has been actually translated into clinical practice. PNI is still an unsolved issue with a marked impact on everyday life of patients, and economic relevance to society. There is a wide field of research to deepen, and future quality clinical studies are needed to provide acceptable scientific evidence. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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Close mobile search navigation Article navigation. This provides first evidence that transplanted genetically modified SC do successfully integrate into the host tissue where they could actively contribute to the regeneration process. The myelination progress was mediated via enhanced brain-derived neurotrophic factor signals, which driving the promyelination effect on SCs at the onset of myelination.
The administration immediately after rat sciatic nerve crush and daily thereafter produced increased nerve regeneration and growth-associated expression.
Neuronal loss and degeneration resulting from peripheral nerve injuries has lead us to explore the possibility of using laser phototherapy on cells as a method of preventing or decreasing this phenomena. My library Help Advanced Book Search. Human umbilical cord-derived mesenchymal stromal cells differentiate into functional Schwann cells that sustain peripheral nerve regeneration. View larger version 74K. Journal of Biophotonics 7:
The neurite outgrowth was significantly higher than the control medium and undifferentiated WJMSCs group. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury. Cells with SC properties and with the ability to support axonal regeneration and reconstruct myelin can be successfully induced from UC-MSCs to promote functional recovery after peripheral nerve injury.
Histomorphometrical and electrophysiological measurements showed significant improvement as compared with diluent controls. Endothelin treatment of PC12 does not cause upregulation of heat shock proteins. Regulation of heat shock proteins after nerve injury is not likely due to endothelin signaling.
Histological analysis shows that fasudil treatment increases the number of regenerating axons with large diameter. The axon count, axon density and nerve fiber diameter within the region of acute crush injury was improved. Regenerated axons partially derived from the proximal motor axons. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.
Sensory and motor functions were significantly improved in treated animals in behavioral tests. There was no significant difference in the motor function between the two groups at 4 weeks. COG significantly promoted axon elongation in primary dorsal root ganglion cultures from rat pups. Fetal NSCs transplanted into peripheral nerves could differentiate into neurons and form functional NMJs with denervated muscle.
IGF-1 also significantly increased myelination and SC activity and preserved the morphology of the postsynaptic neuromuscular junction. However, remyelination of regenerated axons distal to the injury site was considerably improved by the PSA mimetic indicating that effects on SCs in the denervated nerve may underlie the functional effects seen in motor recovery.
SC proliferation in vivo was enhanced in both motor and sensory branches of the femoral nerve by application of the PSA mimetic. Significantly, the combined treatment showed the most beneficial effect. The combined therapy caused the most significantly beneficial effects. However, ES at 4 mA provoked adverse responses to the function recovery of regenerated nerves in the kinematic gait analysis.
ES appears to have a detrimental effect on the regeneration process. Prolonged prothrombin time and reduced fibrinogen but did not change activated partial thromboplastin time and bleeding time. Decreased injury-induced fibrin deposition. The increased production of TNF-alpha and apoptosis were attenuated by natto treatment. The maintenance of activity helps to prevent the development of hyperreflexia.
Although the group that had been given the erythropoietin immediately postinjury showed the best enhancement of recovery, the timing of the administration of the drug was not critical. Histological analysis demonstrated enhanced erythropoietin-receptor positivity in the nerves that recovered fastest, suggesting that accelerated healing correlates with expression of the receptor in nerve tissue.
All neurons in ganglia of crushed nerves that were Sox11 immunopositive showed colabeling for the stress and injury-associated activating transcription factor 3. The static footprint analysis demonstrates no improved or accelerated recovery pattern. The RGTAs strongly reduce nerve adherence to surrounding tissue after nerve crush injury. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers.
Reinnervation of the target muscles in the majority of the treated animals. More intense axonal growth. The administration of erythropoietin in its long-lasting recombinant forms affords significant neuroprotection in peripheral nerve injury models and may hold promise for future clinical applications.
This functional recovery was supported by histological analysis. In the absence of any cellular elements, VEGF-impregnated acellular peripheral nerve grafts do not demonstrate enhanced axonal elongation, as noted by relatively few axons at the distal nerve graft coaptation site. Beginning of re-establishment of active foot movements at fourth month after surgery. However, oral treatment for 4 weeks lead to reduced pain-related behaviour suggesting either slowly developing analgesic actions or enhancement of recovery processes.
Treatment with BRX promotes restoration of morphological and functional properties in the sensory system following peripheral nerve injury. No differences in motor function. For mm nerve defect, nerve regeneration was inferior to that of the control group. Chitosan-collagen film degraded at 12 weeks postoperatively. Equally enhanced the axonal regeneration distance but the quantity of axons was greater using syngeneic SC. Allogenic SC did not induce deleterious immune response. SC continued to express phenotypic markers of non-myelination and these were highest in conduits with allogeneic SC.
At the end of 12 weeks of behavioral testing, there was no difference in motor recovery. Regenerated sciatic nerves from NT3-treated animals had slightly more axons than control- or NGF-treated animals. It has an immediate protective effect. It not only messes with your business, and maybe your users experience, but it can also hurt your digital profile.
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