Advance of Netrin-1 for Protection and Repairment of Injuries after Cerebral Infarction (review) / 中国康复理论与实践

Netrin-1 may protect and repair the damage caused by cerebral infarction, in terms of inhibiting apoptosis and inflammatory, and promoting angiogenesis and axon regeneration, etc. Netrin-1 may associate with the pathogenesis and outcome of cerebral infarction. The application of Netrin-1 in clinic needs more researches.

The effect of rehabilitation training on the expression of neuroglobin in the peri-infarct cortex and its mechanism / 中华物理医学与康复杂志

Objective:To study the effect of rehabilitation training on the expression of neuroglobin (Ngb), oxidative stress and axon regeneration in the cortex and explore possible mechanisms of functional recovery after cerebral infarction.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and a rehabilitation group. Cerebral infarction was modelled in the model and rehabilitation groups using Longa′s middle cerebral artery occlusion (MCAO) technique. The sham operation group received the same procedure except that no thread was inserted to block the middle cerebral artery. The rats in the rehabilitation group began treadmill training 24h after the operation, while the other two groups were left on the treadmill without training. On the 3rd, 7th and 14th days after the operation, all of the rats′ neurological functioning was assessed using modified neurological severity scores (mNSSs). After the last mNSS test, all of the rats were sacrificed and peri-infarct brain tissue was resected to detect the expression of Ngb and oxidative stress indicators including superoxide dismutase (SOD), nitric oxide and malondialdehyde (MDA), as well as neurofilament-200 (NF-200) indicating axon regeneration.Results:On the 3rd day after the surgery there was no significant difference between the average mNSS scores of the rehabilitation and model groups. On the 7th and 14th day the average mNSS score of the rehabilitation group was significantly better than that of the model group. The average expression of Ngb in the model group was significantly higher than in the sham operation group. After the intervention, the average expression of SOD in the rehabilitation group was significantly higher than in the model group, while NO and MDA expression were significantly lower. After the intervention the average expression of NF-200 in the rehabilitation group was also significantly higher than in the model group.Conclusions:Rehabilitation training benefits the recovery of neurological function after cerebral infarction, at least in rats. The mechanism may be related to the upregulation of Ngb, alleviation of oxidative stress and enhancement of axonal regeneration in the peri-infarct cortex.

Research progress on dental pulp stem cells in the repair of peripheral nerve injury / 口腔疾病防治

@#Peripheral nerve injury (PNI) is a common disease in the oral cavity that can easily lead to loss of function and abnormal appearance. The application of dental pulp stem cells (DPSCs) combined with tissue engineering in the repair of PNI is a research hotspot. DPSCs have the advantages of abundant sources, simple extraction, low immunogenicity and a high proliferation rate in vitro. They can differentiate into Schwann cells (SCs). SCs can induce autophagy and secrete key neurotrophic factors, such as nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor and glial cell-derived neurotrophic factor. SCs are beneficial for the repair of nerve injury. DPSCs in different periods have differences in immune regulation, anti-inflammatory effects, expression of neural markers, angiogenesis and so on, which provide more diversified choices for nerve repair. At present, the introduction of tissue engineering provides a more controllable and improved microenvironment for DPSCs, which is conducive to the application and development of DPSCs in regenerative medicine and tissue engineering. However, there are still many problems to be solved, such as the selection of stem cells, functional link recovery, uncontrollable direction of axon regeneration, regulation of the peripheral nervous system and mechanism of repair.

Review of the regeneration mechanism of complete spinal cord injury / 中国修复重建外科杂志

Spinal cord injury (SCI), especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient's quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies. Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common, recovery of some sensory and motor functions post complete SCI include the following three contributing reasons. ① Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets; ② New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps; ③ The combined effect of ① and ②. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.

Research Progress of Electroacupuncture on Axonal Regeneration after Spinal Cord Injury(review) / 中国康复理论与实践

The restoration of motor function after spinal cord injury is a major problem in the medical field,in which axonal regenera-tion is the basis and goal of motor and neurological recovery.Researches showed that electroacupuncture was effective on axonal regenera-tion after spinal cord injury.In this paper,the mechanisms were summarized from the aspects of the formation of glial scar,the role of axon growth inhibitory factor,the secretion of neurotrophic factor and the growth status of neurons.

Application of Two Kinds of Tissue Clearing Method in Observing 3D Imaging of Spinal Cord with Immunofluo-rescent Staining / 中国康复理论与实践

Objective To compare the application of CUBIC and iDISCO clearing methods in observing 3D imaging of spinal cord with immunofluorescent staining. Methods 1 mm thick spinal cord coronal sections were processed with CUBIC and iDISCO, respectively. The neurofilament (NF) protein was detected by immunofluorescent staining and then was observed by a laser confocal microscope. Results Compared with CUBIC, iDISCO had the advantages of shorter time, higher transparency (F=6.64, P<0.01), and deeper penetration (F=5117.55, P<0.01). Conclusion Immunofluorescent staining combined with iDISCO could completely observe the spinal axons with shorter time and better stain effect.

Effects of Jiaji Electroacupuncture and Neurodynamic Mobilization Technique on Axon Regeneration and Con-tent of Neurotrophic Factors in Rabbits with Sciatic Nerve Injury / 中国康复理论与实践

Objective To observe the effects of Jiaji electroacupuncture and neurodynamic mobilization technique on axon regeneration and content of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in rabbits with sciatic nerve injury. Meth-ods 30 male adult rabbits were assigned to sham (A, n=6), model (B, n=6), neurodynamic mobilization (C, n=6), Jiaji electroacupuncture (D, n=6), and Jiaji electroacupuncture combine with neurodynamic mobilization (E, n=6) groups. The group C was treated with neurodynam-ic mobilization, the group D with Jiaji electroacupuncture, and the group D with both 3 days after modeling of clamping at sciatic nerve, while the groups A and B with no treatment. The axon regeneration was observed with HE staining, and the content of BDNF and CNTF in serum was measured with ELISA 4 weeks after treatment. Results The axons regeneration was observed better in the groups C, D and E than in the group B. The content of BDNF and CNTF was more in the groups C, D and E than in the group B (P<0.05). Conclusion Both Ji-aji electroacupuncture and neurodynamic mobilization can improve axon regeneration with synergistic action, which may associate with the increase of BDNF and CNTF in serum.

Microenvironment for Axonal Regeneration after Peripheral Nerve Injury (review) / 中国康复理论与实践

The microenvironment after peripheral nerve injury becomes complicated for axon regeneration, which can be promotion, in-hibition, or both. This paper summarized the researches about the effect of microenvironment on axon regeneration after peripheal nerve in-jury.

Effects of Jiaji Electroacupuncture and Neurodynamic Mobilization Technique on Axon Regeneration and Content of Neurotrophic Factors in Rabbits with Sciatic Nerve Injury / 中国康复理论与实践

@#Objective To observe the effects of Jiaji electroacupuncture and neurodynamic mobilization technique on axon regeneration and content of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in rabbits with sciatic nerve injury. Methods 30 male adult rabbits were assigned to sham (A, n=6), model (B, n=6), neurodynamic mobilization (C, n=6), Jiaji electroacupuncture (D, n=6), and Jiaji electroacupuncture combine with neurodynamic mobilization (E, n=6) groups. The group C was treated with neurodynamic mobilization, the group D with Jiaji electroacupuncture, and the group D with both 3 days after modeling of clamping at sciatic nerve, while the groups A and B with no treatment. The axon regeneration was observed with HE staining, and the content of BDNF and CNTF in serum was measured with ELISA 4 weeks after treatment. Results The axons regeneration was observed better in the groups C, D and E than in the group B. The content of BDNF and CNTF was more in the groups C, D and E than in the group B (P<0.05). Conclusion Both Jiaji electroacupuncture and neurodynamic mobilization can improve axon regeneration with synergistic action, which may associate with the increase of BDNF and CNTF in serum.

Microenvironment for Axonal Regeneration after Peripheral Nerve Injury (review) / 中国康复理论与实践

@#The microenvironment after peripheral nerve injury becomes complicated for axon regeneration, which can be promotion, inhibition, or both. This paper summarized the researches about the effect of microenvironment on axon regeneration after peripheal nerve injury.

Enxerto com tubo de polietileno poroso preenchido com gordura autóloga no reparo de nervo periférico associado com protocolo de imersão em câmara hiperbárica / Graft with porous polyethylene rod filled with autologous adipocytes in peripheral nerve repair associated with immersion in hyperbaric chamber

Os nervos periféricos são extensões do sistema nervoso central e responsável pela interação das atividades entre as extremidades, em suas funções sensitivas e motoras. São vulneráveis aos mesmos tipos de traumas que afetam outros tecidos: contusão, compressão, esmagamento, estiramento, avulsão e laceração. As lesões de nervos periféricos situam-se entre as mais incapacitantes que acometem indivíduos em idade produtiva, em face dos múltiplos aspectos concernentes às sequelas deste tipo de afecção. Desta forma, a interrupção de continuidade da estrutura do nervo, como no caso da neurotmese, por algum tipo de trauma, resulta na interrupção de transmissão dos impulsos nervosos e na desorganização de suas atividades funcionais. Por meio da utilização da microcirurgia foi possível desenvolver técnicas reparadoras que vão desde simples neurorrafia término-terminal até sofisticados procedimentos cirúrgicos com a utilização de enxertos de nervos, veias e artérias invertidas, tubos sintéticos de materiais variados, tais como silicone e polietileno. Outro aspecto que intriga pesquisadores de todo mundo é a utilização de fatores neurogênicos capazes de acelerar ou melhorar a regeneração de nervos periféricos. A gordura autóloga tem sido continuamente referenciada pela sua abundante oferta, no próprio sitio cirúrgico, apresentando resultados promissores, visto que a adventícia dos vasos é constituída por tecido conjuntivo frouxo, rico em adipócitos. Assim, em um trauma, os neuritos oriundos do coto proximal do nervo lesado, ficam diretamente em contato com esses adipócitos. Seguindo este raciocínio, e com base em trabalhos anteriores onde foi usada veia preenchida com músculo esquelético a fresco como enxerto, decidiu-se testar a possibilidade de crescimento axonal por meio de enxerto com tubo de polietileno preenchido por tecido adiposo autólogo associado a protocolo de imersão em câmara hiperbárica, por meio de um estudo Randomizado Controlado...

The peripheral nerves are extensions of the central nervous system and are responsible for the sensory and motor functions of the limbs. These nerves are vulnerable to the same types of traumas that affect other tissues: contusion, compression, crushing, stretching, avulsion, and laceration. Amongst the most disabling kinds of injuries that affect working-age individuals are those of the peripheral nerves; due to the multifaceted characteristics of the aftereffects of the injury. The break in continuity of the nerve structure due to trauma, as in the case of neurotmesis, results in the disruption of the transmission of nerve impulses and the disorganization of their functions. Through the use of microsurgery, it was possible to develop reconstructive techniques that range from a simple end-to-end neurorrhaphy to sophisticated surgical procedures that utilize nerve grafts, inverted veins and arteries, and synthetic rods of varied materials such as silicone or porous polyethylene. Another aspect that intrigues researchers around the world is the utilization of neurogenic factors capable of accelerating or improving the regeneration of peripheral nerves. Autologous fat has been a constant reference in this field of surgery due to its abundant supply at the surgical site itself. The results are promising, as the adventitia of vessels consists of loose connective tissue rich in adipocytes. Thus in a trauma, the neurites derived from the proximal stump of the damaged nerve are in direct contact with these adipocytes. Following this reasoning, and based on previous studies where veins grafted with fresh skeletal muscle were used, we decided to conduct a randomized controlled study to test the possibility of axonal growth by means of grating with a polyethylene rod filled with autologous adipocytes associated with immersion in a hyperbaric chamber. In an attempt to recover the sciatic nerve, a rod 12 mm in length, with a diameter of 0.25 mm, and with pores...

Effect of free NgR-modified bone marrow stromal cell transplantation on axon regeneration after spinal cord injury / 中华物理医学与康复杂志

Objective To evaluate the effect of free NgR-modified bone marrow stromal cell (BMSC) transplantation on axon regeneration in rats after spinal cord injury. Methods Genes encoding free NgR protein were cloned and transduced into BMSCs at passage 3 using a lentivirus vector.Indirect immunofluorescence was used to detect the expression of free NgR protein.Meanwhile a spinal cord contusion model was established in 36 adult Sprague-Dawley rats at the T10 segment.The rats were then divided randomly into an experimental group and a control group.NgR + BMSCs were transplanted into the injured site 1 week post-trauma in the experimental group.BMSCs were also transplanted at the same time into the control group.Expression of free NgR at the injury site was detected by immunohistochemical staining at 1 week post-transplantation.The functional recovery of both groups was evaluated at 4 and 6 weeks post-transplantation.Longitudinal sections of the spinal cord were studied for axon regeneration using horseradish peroxidase staining. Results Expression of free NgR was found in the cell plasma of BMSCs by indirect immunofluorescence post-transfection.Positive immunohistochemical staining for NgR was found at the transplant site in the experimental group 1 week post-transplantation.Better axon plasticity could be observed in the experimental group.The Basso-Beattie-Bresnahan scoring of the experimental group was significantly higher than that of the controls at both observation times. Conclusions Free NgR-modified BMSCs can prompt injured axons to regenerate and thus to promote the recovery of neurological function.This might provide a new strategy to treat spinal cord injury.

Effects of rehabilitation on the axon regeneration microenvironment and motor function after spinal cord injury in beagle dogs / 中华物理医学与康复杂志

Objective To investigate the effects of rehabilitation training on the microenvironment for axon regeneration and the possible mechanisms promoting axon regeneration,reconstruction and functional compensation after spinal cord injury (SCI) in beagle dogs.Methods Fifteen beagles were divided into a sham operated group,an SCI model group and a rehabilitation training group.Spinal cord hemi-transection injury was carried out.From the 8th day after SCI,the rehabilitation training group was given treadmill training.All dogs were sacrificed 60 days postinjury and samples were harvested.Chondroitin sulphate proteoglycan (CSPG) expression of astroglial cells around the injured area was observed using an immunofluorescence technique.The expression of glial fibrillary acidic protein (GFAP) and CSPG protein in each group were semi-quantified by Western blot analysis.Axon regeneration was observed by silver staining.Motor function was assessed using modified Tarlov scores.Results In the rehabilitation training group,compared with the model group astroglial production of CSPG was reduced remarkably.Both CSPG expression and axon regeneration were enhanced and functional deficits improved.Conclusions Rehabilitation training can inhibit astroglial production of CSPG,improve the microenvironment for injured axon regeneration,and promote reconstruction and functional compensation after traumatic SCI.

Mechanism of Nogo and Its Receptors during Repairing of Spinal Cord Injury (review) / 中国康复理论与实践

@# Myelin of the adult mammalian central nervous system(CNS)has been attributed to affect nerve structural plasticity and suppress regeneration of nerve fibers.Nogo-A is possibly the best characterized of a variety of neurite growth inhibitors in CNS myelin.Neutralizing its activity results in improved axon regrowth and functional recovery in experimental spinal cord injury(SCI)models of animals.Nogo-A and its receptors,especially Nogo-66 receptor(NgR),p75 neurotrophin receptor(p75NTR),and LINGO-1 increasingly become the hot spot in the study of SCI repair,and have become the major targets for therapeutic intervention to promote axon regeneration after SCI.Inhibition of Nogo-A and its receptors NgR/p75NTR/LINGO-1 may be promote the regeneration of axon and maximize functional recovery after SCI.

Differentiation of neural stem cells after transplanted into vitreous and the effects on the regeneration of retina ganglion cells / 中国病理生理杂志

AIM: To investigate the differentiation of neural stem cells (NSCs) after transplanted into vitreous and the effects on the regeneration of retina ganglion cells (RGCs) after optic nerve microcrushed.METHODS: After optic nerve microcrushed in adult rat, 2?104/2 ?L NSCs or 2 ?L 0.1 mol/L PBS was injected into vitreous. Animals were divided into control group (MC group, MC+PBS group) and experiment group (MC+NSCs). Animals in each group were allowed to survive for 3, 4, 5 weeks, respectively. The regenerating RGCs were labeled retrogradely with granular blue, and the numbers of regenerating RGCs in each retina were observed under fluorescent microscope. In addition after 5 animals in MC+NSCs group survived for 4 weeks, rat eyeballs were removed and prepared as freezing microtome sections for observing the migration of NSCs and NF, GFAP, CNP immumodetection.RESULTS: Compared the mean numbers of regenerating RGCs between experiment group and control group at 3, 4, 5 weeks, the difference was significant (P