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1.
Science ; 368(6498): 1428-1429, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32587008
2.
Acta Cir Bras ; 35(4): e202000405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555937

RESUMO

PURPOSE: To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. METHODS: A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. RESULTS: There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). CONCLUSION: Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Tecido Nervoso/transplante , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/cirurgia , Animais , Fenômenos Biomecânicos , Eletromiografia , Masculino , Regeneração Nervosa/fisiologia , Tecido Nervoso/citologia , Coelhos , Valores de Referência , Reprodutibilidade dos Testes , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Resultado do Tratamento
3.
Nature ; 581(7806): 77-82, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32376949

RESUMO

Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury1; however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their 'regenerative transcriptome' after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome; deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.


Assuntos
Proliferação de Células/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Regeneração Nervosa/genética , Células-Tronco Neurais/citologia , Neurônios/metabolismo , Neurônios/patologia , Transcrição Genética , Animais , Axônios/patologia , Axônios/fisiologia , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Proteína Huntingtina/genética , Camundongos , Células-Tronco Neurais/transplante , Plasticidade Neuronal , Neurônios/citologia , Neurônios/transplante , Biossíntese de Proteínas , Tratos Piramidais/citologia , Tratos Piramidais/metabolismo , Tratos Piramidais/patologia , RNA-Seq , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Transcriptoma
7.
PLoS Biol ; 18(3): e3000657, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163406

RESUMO

While many regulators of axon regeneration have been identified, very little is known about mechanisms that allow dendrites to regenerate after injury. Using a Drosophila model of dendrite regeneration, we performed a candidate screen of receptor tyrosine kinases (RTKs) and found a requirement for RTK-like orphan receptor (Ror). We confirmed that Ror was required for regeneration in two different neuron types using RNA interference (RNAi) and mutants. Ror was not required for axon regeneration or normal dendrite development, suggesting a specific role in dendrite regeneration. Ror can act as a Wnt coreceptor with frizzleds (fzs) in other contexts, so we tested the involvement of Wnt signaling proteins in dendrite regeneration. We found that knockdown of fz, dishevelled (dsh), Axin, and gilgamesh (gish) also reduced dendrite regeneration. Moreover, Ror was required to position dsh and Axin in dendrites. We recently found that Wnt signaling proteins, including dsh and Axin, localize microtubule nucleation machinery in dendrites. We therefore hypothesized that Ror may act by regulating microtubule nucleation at baseline and during dendrite regeneration. Consistent with this hypothesis, localization of the core nucleation protein γTubulin was reduced in Ror RNAi neurons, and this effect was strongest during dendrite regeneration. In addition, dendrite regeneration was sensitive to partial reduction of γTubulin. We conclude that Ror promotes dendrite regeneration as part of a Wnt signaling pathway that regulates dendritic microtubule nucleation.


Assuntos
Dendritos/fisiologia , Proteínas de Drosophila/metabolismo , Regeneração Nervosa/fisiologia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Animais , Drosophila , Proteínas de Drosophila/genética , Microtúbulos/genética , Microtúbulos/metabolismo , Mutação , Neurônios/fisiologia , Interferência de RNA , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Wnt/genética , Receptores Wnt/metabolismo , Via de Sinalização Wnt
8.
Nat Neurosci ; 23(3): 337-350, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32112058

RESUMO

Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. Our data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.


Assuntos
Macrófagos/fisiologia , Microglia/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Traumatismos da Medula Espinal/patologia , Cicatrização/fisiologia , Animais , Axônios/fisiologia , Microambiente Celular , Locomoção/fisiologia , Camundongos , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Vias Neurais/fisiologia , Fagocitose , Recuperação de Função Fisiológica , Sensação/fisiologia , Traumatismos da Medula Espinal/metabolismo
9.
Klin Monbl Augenheilkd ; 237(2): 128-132, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32040975

RESUMO

The development of neuroprotective and regenerative therapies in the central nervous system (CNS) poses a major challenge in clinical and basic research. In contrast to the peripheral nervous system, which has a comparatively high intrinsic regenerative capacity, this characteristic is poorly developed in the adult CNS. In this review, some basic growth mechanisms of CNS neurons will be highlighted, as well as factors that prevent successful regeneration after injury. Primarily in the context of glaucoma, preclinical and clinical studies are presented which can improve the understanding of neurodegenerative processes in the optical system and thus provide the basis for current and future therapeutic strategies.


Assuntos
Sistema Nervoso Central , Neuroproteção , Glaucoma , Humanos , Regeneração Nervosa , Neurônios
10.
Nat Rev Neurol ; 16(4): 229-240, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32099190

RESUMO

Spinal cord injury (SCI) remains one of the biggest challenges in the development of neuroregenerative therapeutics. Cell transplantation is one of numerous experimental strategies that have been identified and tested for efficacy at both preclinical and clinical levels in recent years. In this Review, we briefly discuss the state of human olfactory cell transplantation as a therapy, considering both its current clinical status and its limitations. Furthermore, we introduce a mesenchymal stromal cell derived from human olfactory tissue, which has the potential to induce multifaceted reparative effects in the environment within and surrounding the lesion. We argue that no single therapy will be sufficient to treat SCI effectively and that a combination of cell-based, rehabilitation and pharmaceutical interventions is the most promising approach to aid repair. For this reason, we also introduce a novel pharmaceutical strategy based on modifying the activity of heparan sulfate, an important regulator of a wide range of biological cell functions. The multi-target approach that is exemplified by these types of strategies will probably be necessary to optimize SCI treatment.


Assuntos
Heparitina Sulfato/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Mucosa Olfatória/citologia , Traumatismos da Medula Espinal/terapia , Regeneração da Medula Espinal , Transplante de Células/métodos , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Heparina/uso terapêutico , Heparitina Sulfato/análogos & derivados , Humanos , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa , Neuroglia , Mucosa Olfatória/fisiologia , Neurônios Receptores Olfatórios
11.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(1): 59-68, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32037768

RESUMO

OBJECTIVE: To systematically evaluate the repairing effect of stem cells on facial nerve defects. METHODS: Articles regarding the regenerating effect of stem cells on facial nerves in animals were collected from the databases of Pubmed, Cochrane Library, Web of Science, Embase, Scopus, and CBM. Two professionals independently completed the article screening, data extraction, and bias risk assessment. RevMan 5.3 and random-effects models were used for the statistical analysis, and the results were presented in the form of mean differences (MD) with a 95%CI. The results of functional evaluation (vibrissae movement, facial paralysis) and histological evaluation (density of myelinated fibers, diameter of fibers, thickness of myelin sheath, G ratio) of facial nerve were Meta-analyzed. RESULTS: A total of 4 614 articles were retrieved from the 6 databases, and 15 of these articles were included in the Meta-analysis. For vibrissae movement and facial paralysis, the stem cell group scored significantly higher than the non-stem cell group (P<0.05). The density of myelinated fibers and thickness of the myelin sheath in the stem cell group were higher than those in the non-stem cell group (P<0.05). The G ratio in the stem cell group was smaller than that in the non-stem cell group (P=0.001). There was no significant difference in fiber diameter (P=0.08). CONCLUSIONS: Stem cells have potential in promoting facial nerve regeneration.


Assuntos
Nervo Facial , Paralisia Facial , Animais , Regeneração Nervosa , Células-Tronco , Vibrissas
12.
Invest Ophthalmol Vis Sci ; 61(2): 31, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32084268

RESUMO

Purpose: To investigate the possible role of activating transcription factor 3 (ATF3) in retinal ganglion cell (RGC) neuroprotection and optic nerve regeneration after optic nerve crush (ONC). Methods: Overexpression of proteins of interest (ATF3, phosphatase and tensin homolog [PTEN], placental alkaline phosphatase, green fluorescent protein) in the retina was achieved by intravitreal injections of recombinant adenovirus-associated viruses (rAAVs) expressing corresponding proteins. The number of RGCs and αRGCs was evaluated by immunostaining retinal sections and whole-mount retinas with antibodies against RNA binding protein with multiple splicing (RBPMS) and osteopontin, respectively. Axonal regeneration was assessed via fluorophore-coupled cholera toxin subunit B labeling. RGC function was evaluated by recording positive scotopic threshold response. Results: The level of ATF3 is preferentially elevated in osteopontin+/RBPMS+ αRGCs following ONC. Overexpression of ATF3 by intravitreal injection of rAAV 2 weeks before ONC promoted RBPMS+ RGC survival and preserved RGC function as assessed by positive scotopic threshold response recordings 2 weeks after ONC. However, overexpression of ATF3 and simultaneous downregulation of PTEN, a negative regulator of the mTOR pathway, combined with ONC, only moderately promoted short distance RGC axon regeneration (200 µm from the lesion site) but did not provide additional RGC neuroprotection compared with PTEN downregulation alone. Conclusions: These results reveal a neuroprotective effect of ATF3 in the retina following injury and identify ATF3 as a promising agent for potential treatments of optic neuropathies.


Assuntos
Fator 3 Ativador da Transcrição/fisiologia , Neuroproteção/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , Células Ganglionares da Retina/fisiologia , Fator 3 Ativador da Transcrição/metabolismo , Animais , Axônios/patologia , Camundongos , Camundongos Endogâmicos C57BL , Compressão Nervosa , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/patologia , Células Ganglionares da Retina/patologia
13.
Int J Nanomedicine ; 15: 315-332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021182

RESUMO

Purpose: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.


Assuntos
Astrócitos/fisiologia , Condroitina ABC Liase/metabolismo , Nanopartículas de Magnetita/uso terapêutico , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Animais , Astrócitos/citologia , Axônios/efeitos dos fármacos , Movimento Celular , Células Cultivadas , Condroitina ABC Liase/genética , Condroitina ABC Liase/farmacologia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Feminino , Campos Magnéticos , Nanopartículas de Magnetita/química , Masculino , Regeneração Nervosa/efeitos dos fármacos , Polietilenoimina/química , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Traumatismos da Medula Espinal/terapia
14.
Biochemistry (Mosc) ; 85(Suppl 1): S108-S130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32087056

RESUMO

It had been commonly believed for a long time, that once established, degeneration of the central nervous system (CNS) is irreparable, and that adult person merely cannot restore dead or injured neurons. The existence of stem cells (SCs) in the mature brain, an organ with minimal regenerative ability, had been ignored for many years. Currently accepted that specific structures of the adult brain contain neural SCs (NSCs) that can self-renew and generate terminally differentiated brain cells, including neurons and glia. However, their contribution to the regulation of brain activity and brain regeneration in natural aging and pathology is still a subject of ongoing studies. Since the 1970s, when Fuad Lechin suggested the existence of repair mechanisms in the brain, new exhilarating data from scientists around the world have expanded our knowledge on the mechanisms implicated in the generation of various cell phenotypes supporting the brain, regulation of brain activity by these newly generated cells, and participation of SCs in brain homeostasis and regeneration. The prospects of the SC research are truthfully infinite and hitherto challenging to forecast. Once researchers resolve the issues regarding SC expansion and maintenance, the implementation of the SC-based platform could help to treat tissues and organs impaired or damaged in many devastating human diseases. Over the past 10 years, the number of studies on SCs has increased exponentially, and we have already become witnesses of crucial discoveries in SC biology. Comprehension of the mechanisms of neurogenesis regulation is essential for the development of new therapeutic approaches for currently incurable neurodegenerative diseases and neuroblastomas. In this review, we present the latest achievements in this fast-moving field and discuss essential aspects of NSC biology, including SC regulation by hormones, neurotransmitters, and transcription factors, along with the achievements of genetic and chemical reprogramming for the safe use of SCs in vitro and in vivo.


Assuntos
Envelhecimento/metabolismo , Regeneração Nervosa/fisiologia , Células-Tronco Neurais/metabolismo , Doenças Neurodegenerativas/terapia , Adulto , Animais , Transplante de Células/efeitos adversos , Transplante de Células/métodos , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Epigênese Genética , Hormônios/metabolismo , Hormônios/farmacologia , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Doenças Neurodegenerativas/metabolismo , Neurogênese , Neurotransmissores/metabolismo , Neurotransmissores/farmacologia , Fatores de Transcrição/metabolismo
15.
PLoS Biol ; 18(1): e3000585, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905199

RESUMO

It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here, by performing single-cell transcriptomics, we found that amyloid toxicity-induced interleukin-4 (IL4) promotes NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of serotonin. NSC proliferation was suppressed by serotonin via down-regulation of brain-derived neurotrophic factor (BDNF)-expression in serotonin-responsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via nerve growth factor receptor A (NGFRA)/ nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB) signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after AD conditions in zebrafish.


Assuntos
Doença de Alzheimer , Comunicação Celular/fisiologia , Regeneração Nervosa/fisiologia , Neurogênese/fisiologia , Neuroglia/fisiologia , Neurônios/fisiologia , Fatores Etários , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Animais Geneticamente Modificados , Encéfalo/metabolismo , Encéfalo/fisiologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Transgênicos , Regeneração Nervosa/genética , Células-Tronco Neurais/patologia , Células-Tronco Neurais/fisiologia , Neuroimunomodulação/fisiologia , Plasticidade Neuronal/fisiologia , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Serotonina/genética , Serotonina/metabolismo , Transdução de Sinais/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
16.
Invest Ophthalmol Vis Sci ; 61(1): 4, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31999819

RESUMO

Purpose: Neurotrophic keratopathy is a degenerative disease that may be improved by nerve growth factor (NGF). Our aim was to investigate the use of pergolide, a dopamine (D1 and D2) receptor agonist known to increase the synthesis and release of NGF for regeneration of damaged corneal nerve fibers. Methods: Pergolide function was evaluated by measuring axon length and NGF levels by enzyme-linked immunosorbent assay in cultured chicken dorsal root ganglion (DRG) cells with serial doses of pergolide (10, 25, 50, 150, and 300 µg/ml) and with different concentrations of a D1 antagonist. Pergolide function was further evaluated by cornea nerve fiber density and wound healing in a cornea scratch mouse model. Results: Pergolide increased DRG axon length significantly at a dose between 50 and 300 µg/ml. Different concentrations of D1 antagonist (12, 24, 48, and 96 µg/ml) inhibited DRG axon length growth with pergolide (300 µg/ml). Pergolide (50 µg/ml) upregulated NGF expression in DRG cells at both 24 hours and 48 hours. Pergolide improved cornea nerve fiber density at both 1 week and 2 weeks. Pergolide also improved cornea wound healing. Conclusions: We demonstrated that pergolide can act to promote an increase in NGF which promotes corneal nerve regeneration and would therefore improve corneal sensation and visual acuity in eyes with peripheral neurotrophic keratopathy.


Assuntos
Lesões da Córnea/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Fibras Nervosas/efeitos dos fármacos , Pergolida/uso terapêutico , Animais , Axônios/efeitos dos fármacos , Galinhas , Agonistas de Dopamina/farmacologia , Gânglios Espinais/efeitos dos fármacos , Camundongos , Regeneração Nervosa , Pergolida/farmacologia , Cicatrização/fisiologia
17.
Neuron ; 105(2): 207-209, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31972142

RESUMO

In this issue of Neuron, Yang et al. (2020) identify glycerolipid metabolism as a neuron-intrinsic mechanism that regulates axonal growth and regeneration. Shifting glycerolipid metabolism toward increased triglyceride synthesis blocks PNS neuron regeneration, whereas shifting it toward membrane phospholipid synthesis overcomes regeneration failure in CNS neurons.


Assuntos
Axônios , Regeneração Nervosa , Neurônios
18.
Plast Reconstr Surg ; 145(2): 368e-381e, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985643

RESUMO

BACKGROUND: Acellular nerve allografts are a viable treatment modality for bridging nerve gaps. Several small studies have demonstrated results equal to those of autologous grafts; however, there is information lacking with regard to outcomes for wider indications. The authors evaluated the outcomes of patients treated with a nerve allograft in a variety of clinical situations. METHODS: A retrospective chart analysis was completed between April of 2009 and October of 2017. Inclusion criteria were age 18 years or older at the time of surgery and treatment with a nerve allograft. Patients were excluded if they had not been followed up for a minimum of 6 months. The modified Medical Research Council Classification was used to monitor motor and sensory changes in the postoperative period. RESULTS: Two hundred seven nerve allografts were used in 156 patients; of these, 129 patients with 171 nerve allografts fulfilled the inclusion criteria. Seventy-seven percent of patients achieved a sensory outcome score of S3 or above and 36 percent achieved a motor score of M3 or above. All patients with chronic pain had improvement of their symptoms. Graft length and diameter were negatively correlated with reported outcomes. One patient elected to undergo revision surgery, and the original graft was shown histologically to have extensive central necrosis. Anatomically, allografts used for lower limb reconstruction yielded the poorest results. All chronic patients had a significantly lower postoperative requirement for analgesia, and allografts were effective in not only reducing pain but also restoring a functional level of sensation. CONCLUSIONS: This study supports the wider application of allografts in managing nerve problems. However, caution must be applied to the use of long grafts with larger diameters. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Traumatismos dos Nervos Periféricos/cirurgia , Nervos Periféricos/transplante , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regeneração Nervosa/fisiologia , Neuralgia/cirurgia , Estudos Retrospectivos , Adulto Jovem
19.
Life Sci ; 243: 117308, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954163

RESUMO

Compromised functional regains in about half of the patients following surgical nerve repair pose a serious socioeconomic burden to the society. Although surgical strategies such as end-to-end neurorrhaphy, nerve grafting and nerve transfer are widely applied in distal injuries leading to optimal recovery; however in proximal nerve defects functional outcomes remain unsatisfactory. Biomedical engineering approaches unite the efforts of the surgeons, engineers and biologists to develop regeneration facilitating structures such as extracellular matrix based supportive polymers and tubular nerve guidance channels. Such polymeric structures provide neurotrophic support from injured nerve stumps, retard the fibrous tissue infiltration and guide regenerating axons to appropriate targets. The development and application of nerve guidance conduits (NGCs) to treat nerve gap injuries offer clinically relevant and feasible solutions. Enhanced understanding of the nerve regeneration processes and advances in NGCs design, polymers and fabrication strategies have led to developing modern NGCs with superior regeneration-conducive capacities. Current review focuses on the advances in surgical and engineering approaches to treat peripheral nerve injuries. We suggest the incorporation of endothelial cell growth promoting cues and factors into the NGC interior for its possible enhancement effects on the axonal regeneration process that may result in substantial functional outcomes.


Assuntos
Traumatismos dos Nervos Periféricos/terapia , Animais , Materiais Biocompatíveis , Humanos , Regeneração Nervosa/fisiologia
20.
PLoS One ; 15(1): e0221851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31961897

RESUMO

BACKGROUND: There is currently no effective treatment for promoting regeneration of injured nerves in patients who have sustained injury to the central nervous system such as spinal cord injury. Chondroitinase ABC is an enzyme, which promotes neurite outgrowth and regeneration. It has shown considerable promise as a therapy for these conditions. The aim of the study is to determine if targeting chondroitinase ABC expression to the neuronal axon can further enhance its ability to promote axon outgrowth. Long-distance axon regeneration has not yet been achieved, and would be a significant step in attaining functional recovery following spinal cord injury. METHODOLOGY/PRINCIPAL FINDINGS: To investigate this, neuronal cultures were transfected with constructs encoding axon-targeted chondroitinase, non-targeted chondroitinase or GFP, and the effects on neuron outgrowth and sprouting determined on substrates either permissive or inhibitory to neuron regeneration. The mechanisms underlying the observed effects were also explored. Targeting chondroitinase to the neuronal axon markedly enhances its ability to promote neurite outgrowth. The increase in neurite length is associated with an upregulation of ß-integrin staining at the axonal cell surface. Staining for phosphofocal adhesion kinase, is also increased, indicating that the ß-integrins are in an activated state. Expression of chondroitinase within the neurons also resulted in a decrease in expression of PTEN and RhoA, molecules which present a block to neurite outgrowth, thus identifying two of the pathways by which ChABC promotes neurite outgrowth. CONCLUSIONS / SIGNIFICANCE: The novel finding that targeting ChABC to the axon significantly enhances its ability to promote neurite extension, suggests that this may be an effective way of promoting long-distance axon regeneration following spinal cord injury. It could also potentially improve its efficacy in the treatment of other pathologies, where it has been shown to promote recovery, such as myocardial infarction, stroke and Parkinson's disease.


Assuntos
Condroitina ABC Liase/genética , Regeneração Nervosa/genética , Crescimento Neuronal/genética , Traumatismos da Medula Espinal/genética , Animais , Axônios/metabolismo , Condroitina ABC Liase/antagonistas & inibidores , Regulação da Expressão Gênica/genética , Humanos , Neuritos/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , PTEN Fosfo-Hidrolase/genética , Recuperação de Função Fisiológica/genética , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Proteína rhoA de Ligação ao GTP/genética
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