Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury

Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.     

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.     

Rebuilding motor function of the spinal cord based on functional electrical stimulation

Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the correspond-ing muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip lfexion, ankle plantarlfexion, and ankle dorsilfexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.     

Electrical stimulation modulates injury potentials in rats after spinal cord injury

An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves.Its initial amplitude is a significant indicator of the severity of spinal cord injury,and many cations,such as sodium and calcium,account for the major portion of injury potentials.This injury potential,as well as injury current,can be modulated by direct current field stimulation;however,the appropriate parameters of the electrical field are hard to define.In this paper,injury potential is used as a parameter to adjust the intensity of electrical stimulation.Injury potential could be modulated to slightly above 0 mV(as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections,or around -70 mV,which is resting membrane potential(as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group.In addition,rats receiving no electrical stimulation were used as the control group.Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value,whether the anodes or the cathodes were placed at the site of injury.This phenomenon illustrates that by changing the polarity of the electrical field,electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury.This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.     

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30-180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in- creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potentia~ ~atency can reflect the degree of spinat cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury.     

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T_(9–10) site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.     

Impaired facilitation of motor evoked potentials in incomplete spinal cord injury

Objectives To improve the diagnosis of damaged spinal motor pathways in incomplete spinal cord injury (iSCI) by assessing the facilitation of lower limbs motor evoked potentials (MEP). Methods Control subjects (n = 12) and iSCI patients (n = 21) performed static and dynamic isometric foot dorsiflexions. MEPs induced by transcranial magnetic stimulation and EMG background of tibialis anterior muscle (TA) were analyzed. Static and dynamic muscle activation was performed at comparable levels of maximal voluntary contraction (MVC). The influence of the motor tasks on the excitability and facilitation of MEPs was compared between controls and iSCI patients. Results In the controls an increased facilitation of TA MEP at lower levels of dynamic compared with static activation (10–20% MVC) could be shown. At matched EMG background level the MEP responses were significantly increased. In the iSCI patients at a comparable level of TA activation the MEP responses were significantly reduced and 3 different patterns of MEP responses could be distinguished: i) preserved increment of TA MEP in the dynamic motor task, ii) unchanged MEP size in the dynamic and static motor task, and iii) elicitable MEPs in the dynamic motor task,which were abolished in the static motor task. Conclusions Static and dynamic motor tasks have different effects on TA MEP facilitation. The task–dependent modulation of TA MEPs is comparable to that described for upper limb muscles. Complementary to the MEP delay this approach allows for an estimation of the severity of spinal tract damage. The task–dependent modulation of TA MEPs is an additional diagnostic tool to improve the assessment and monitoring of motor function in iSCI.     

Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

A large body of evidence shows that spinal circuits are significantly affected by training,and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection.However,after incomplete lesions,the effect of treadmill training has been debated,which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects.In this study,rats with moderate spinal cord contusion were subjected to either step training on a treadmill or used in the model(control) group.The treadmill training began at day 7 post-injury and lasted 20 ± 10 minutes per day,5 days per week for 10 weeks.The speed of the treadmill was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat.After 3 weeks of step training,the step training group exhibited a significantly greater improvement in the Basso,Beattie and Bresnahan score than the model group.The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury,while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups.These results suggest that treadmill training significantly improves functional recovery and neural plasticity after incomplete spinal cord injury.     

Effect of the combination of high-frequency repetitive magnetic stimulation and neurotropin on injured sciatic nerve regeneration in rats

Repetitive magnetic stimulation is effective for treating posttraumatic neuropathies following spinal or axonal injury.Neurotropin is a potential treatment for nerve injuries like demyelinating diseases.This study sought to observe the effects of high-frequency repetitive magnetic stimulation,neurotropin and their combined use in the treatment of peripheral nerve injury in 32 adult male Sprague-Dawley rats.To create a sciatic nerve injury model,a 10 mm-nerve segment of the left sciatic nerve was cut and rotated through 180°and each end restored continuously with interrupted sutures.The rats were randomly divided into four groups.The control group received only a reversed autograft in the left sciatic nerve with no treatment.In the high-frequency repetitive magnetic stimulation group,peripheral high-frequency repetitive magnetic stimulation treatment(20 Hz,20 min/d)was delivered for 10 consecutive days after auto-grafting.In the neurotropin group,neurotropin therapy(0.96 NU/kg per day)was administrated for 10 consecutive days after surgery.In the combined group,the combination of peripheral high-frequency repetitive magnetic stimulation(20 Hz,20 min/d)and neurotropin(0.96 NU/kg per day)was given for 10 consecutive days after the operation.The Basso-Beattie-Bresnahan locomotor rating scale was used to assess the behavioral recovery of the injured nerve.The sciatic functional index was used to evaluate the recovery of motor functions.Toluidine blue staining was performed to determine the number of myelinated fibers in the distal and proximal grafts.Immunohistochemistry staining was used to detect the length of axons marked by neurofilament 200.Our results reveal that the Basso-Beattie-Bresnahan locomotor rating scale scores,sciatic functional index,the number of myelinated fibers in distal and proximal grafts were higher and axon lengths were longer in the high-frequency repetitive magnetic stimulation,neurotropin and combined groups compared with the control group.These measures were not significantly different among the high-frequency repetitive magnetic stimulation,neurotropin and combined groups.Therefore,our results suggest that peripheral high-frequency repetitive magnetic stimulation or neurotropin can promote the repair of injured sciatic nerves,but their combined use seems to offer no significant advantage.This study was approved by the Animal Ethics Committee of the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University,China on December 23,2014(approval No.2014keyan002-01).     

Senegenin inhibits neuronal apoptosis after spinal cord contusion injury

Senegenin has been shown to inhibit neuronal apoptosis, thereby exerting a neuroprotective effect. In the present study, we established a rat model of spinal cord contusion injury using the modiifed Allen’s method. Three hours after injury, senegenin (30 mg/g) was injected into the tail vein for 3 consecutive days. Senegenin reduced the size of syringomyelic cavities, and it substantially reduced the number of apop-totic cells in the spinal cord. At the site of injury, Bax and Caspase-3 mRNA and protein levels were decreased by senegenin, while Bcl-2 mRNA and protein levels were increased. Nerve ifber density was increased in the spinal cord proximal to the brain, and hindlimb motor function and electrophysiological properties of rat hindlimb were improved. Taken together, our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury.     

Impulse magnetic stimulation facilitates synaptic regeneration in rats following sciatic nerve injury

The current studies describing magnetic stimulation for treatment of nervous system diseases mainly focus on transcranial magnetic stimulation and rarely focus on spinal cord magnetic stimula-tion.Spinal cord magnetic stimulation has been confirmed to promote neural plasticity after injuries of spinal cord,brain and peripheral nerve.To evaluate the effects of impulse magnetic stimulation of the spinal cord on peripheral nerve regneration,we compressed a 3 mm segment located in the middle third of the hip using a sterilized artery forceps to induce ischemia.Then,all animals un-derwent impulse magnetic stimulation of the lumbar portion of spinal crod and spinal nerve roots daily for 1 month.Electron microscopy results showed that in and below the injuryed segment,the inflammation and demyelination of neural tissue were alleviated,apoptotic cells were reduced,and injured Schwann cells and myelin fibers were repaired.These findings suggest that high-frequency impulse magnetic stimulation of spinal cord and corresponding spinal nerve roots promotes synaptic regeneration following sciatic nerve injury.     

Electrical stimulation and denervated muscles after spinal cord injury

Spinal cord injury(SCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous tissue.These morphological changes may put individuals with SCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and osteoporosis.Currently,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in SCI individuals with lower motor neuron denervation.We,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following SCI.Long pulse width stimulation(LPWS)technique is an upcoming method of stimulating denervated muscles.Our primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated muscle.Stimulation parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and contraction.The use of electrical stimulation in animal and human models induces muscle hypertrophy.Findings in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle function.Human studies have shown similar outcomes,identifying the use of LPWS as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle function.Therefore,displaying promise is an effective future stimulation intervention.In summary,LPWS is a novel stimulation technique for denervated muscles in humans with SCI.Successful studies on LPWS of denervated muscles will help in translating this stimulation technique to the clinical level as a rehabilitation intervention after SCI.     

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation

Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.     

Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).     

Carbon filaments direct the growth of postlesional plastic axons after spinal cord injury

The effect of implantation of carbon filaments and fetal tissues on the axonal regeneration following contusion injury in a rat model was investigated by in situ immunofluorescence. Female Sprague-Dawley rats were subjected to severe contusion injury to the spinal cord at T9-T10. All animals were divided into 5 groups (N = 5/group): normal controls. surgical controls, with carbon filament implants, with fetal tissue implants and with implants consisting of fetal tissue cocultured with carbon filaments. After a 10-week survival period, the astroglial response was assessed by immunoreactive glial fibrillary acidic protein and the neuro-axonal profile by immunoreactive phosphorylated and nonphosphorylated neurofilament proteins. The contusion injury resulted in: (a) dramatically increased immunoreactivity of glial fibrillary acidic protein indicating injury-associated reactive astrogliosis, (b) increase in immunoreactive phosphorylated neurofilament protein indicating upregulated phosphorylation of neurofilament protein, (c) with no change in the highly differentiated nonphosphorylated neurofilament protein which normally occur in the nonregenerating mature neurons. Implantation of fetal tissues alone following contusion injury did not show any appreciable change with regard to the immunoreactivities for the glial and neuronal markers studied, compared to the injury controls. However, the implantation of carbon filaments alone or together with fetal tissues directed the growth of glial fibrillary acidic protein-positive astroglia and phosphoneurofilament-positive neurites along the carbon fibers, with no effect on nonphosphoneurofilament protein. In conclusion, implantation of carbon filaments appears to be critical for facilitating the attachment of astroglia forming a substrate and scaffolding that can further support and direct the growth of postlesional plastic axons across the lesion. In addition, carbon filament prostheses in combination with fetal tissue implants provides an improved combinational approach to promote regrowth of injured neurons following injury.     

Nerve grafting from spinal cord to spinal nerve: a microsurgical technique in cats

A ventral surgical approach is described for the grafting of autologous saphenous nerves between the spinal cord and the avulsed C7 ventral root in the cat. To overcome serious blood loss from the epidural venous plexus, the cats were hyperventilated (end tidal

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to about 23 mmHg) and controlled hypotension was induced (mean arterial pressure to about 60 mmHg). After selective avulsion of the ventral rootlets C7 the saphenous grafts were implanted into the spinal cord and coaptated to the avulsed spinal nerve. The combination of advanced anesthetic methods and microsurgical techniques appeared to be mandatory to achieve a low surgical mortality. Regenerated axons were retrogradely traced using retrograde horseradish peroxidase (HRP), and their functional recovery was evaluated by means of electrophysiological methods.     

Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury

Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.     

Transplantation of olfactory ensheathing cells promotes axonal regeneration in a rat model of spinal cord injury

BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE:To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS:OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS:Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups:sham-surgery (n = 3),surgery (n = 9),and OEC transplantation (n = 11).Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL (1 × 105 cells) cell suspension.MAIN OUTCOME MEASURES:Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS:At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin- or ascending calcitonin gene-related peptideconiaining axons stopped at the fibrotic scar that was formed in the lesion site.At week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION:OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.