The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To circumvent these barriers, biomaterial scaffolds are applied to bridge the lesion gaps for the regrowing axons to follow, and, often by combining stem cell transplantation, to enable the local environment in the growth-supportive direction. Manipulations, such as the modulation of PTEN/mTOR pathways, can also enhance intrinsic CNS axon regrowth after injury. Given the complex pathophysiology of SCI, combining biomaterial scaffolds and genetic manipulation may provide synergistic effects and promote maximal axonal regrowth. Future directions will primarily focus on the translatability of these approaches and promote therapeutic avenues toward the functional rehabilitation of patients with SCIs.
Animals ; Axons ; physiology ; Biocompatible Materials ; Genetic Enhancement ; methods ; Humans ; Nerve Regeneration ; PTEN Phosphohydrolase ; metabolism ; Recovery of Function ; Spinal Cord Injuries ; physiopathology ; Tissue Engineering ; methods ; Tissue Scaffolds

To investigate the role of p38MAPK signal pathway in spinal cord and dorsal root ganglion (DRG) in rats with phantom limb pain and the effects of specific inhibitors.
 Methods: Healthy adult male SD rats (n=48) were cut off one side of the sciatic under anesthesia to establish a model of phantom limb pain. In addition, the healthy rats were taken as a sham group (group S, n=24). The animals were scored by observing the action of chewing (0=no chewing, 13=the worst chewing) after the operation and were sacrificed on the following day after the operation. The successful model of phantom limb pain were randomly divided into 2 groups: a phantom limb pain group (group P, n=24) and a phantom limb pain plus inhibitor group (group P+I, n=24). SB203580 was given to the rat at 0.8 mg/kg on every Monday until the rats were sacrificed, the rest of the rats received an equal amount of saline. Eight rats from each group were randomly taken for the determination of levels of P-p38MAPK in spinal cord and DRG before administration and on the 4th, 6th, 8th weekend following the administration, respectively.
 Results: In the sham group, no animal developed chewing. Meanwhile, rats in successful model of phantom limb pain group began chewing from the 2nd day after operation with scores at eight to eleven. The chewing scores in the P+I group were reduced after the treatment. Compared with group S, P-p38MAPK levels were elevated in groups of P and P+I (P<0.05 or P<0.01). Compared with group P, P-p38MAPK level was decreased in the group P+I (P<0.05 or P<0.01).
 Conclusion: P38MAPK signal pathway involves in the development of phantom limb pain.
Animals ; Disease Models, Animal ; Enzyme Inhibitors ; pharmacology ; Ganglia, Spinal ; enzymology ; Imidazoles ; pharmacology ; Male ; Mastication ; physiology ; Phantom Limb ; enzymology ; etiology ; physiopathology ; Pyridines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; Self Mutilation ; enzymology ; physiopathology ; Signal Transduction ; Spinal Cord ; enzymology ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

Ischemic neurological injury is the most feared complication of spinal deformity surgery.In recent years, more attention has been paid to ischemic neurological injury during spinal deformity surgery including causes, risk factors, and prevention. The direct and indirect causes of ischemic neurological injury contains ligature of the segmental arteries, perioperative bleeding and excessive stretching or shortening of the spinal cord.Those patients at greatest risk for paraplegia following diagnosis of thoracic kyphosis or kyphoscoliosis, unilateral vessel ligation, perioperative hypotension, and extensive anterior and posterior surgery. Keeping reasonable mean arterial pressure and multimodal intraoperative monitoring may effectively prevent ischemic neurologic injury during surgery for spinal deformity.
Arteries ; Humans ; Ischemia ; physiopathology ; Kyphosis ; surgery ; Ligation ; Monitoring, Intraoperative ; Neurosurgical Procedures ; adverse effects ; Paraplegia ; Risk Factors ; Scoliosis ; surgery ; Spinal Cord Injuries

OBJECTIVETo study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI).

METHODSOne hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8).

RESULTSIn SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP.

Animals ; Colon ; physiopathology ; Electric Stimulation Therapy ; Epithelial Cells ; drug effects ; Intestinal Mucosa ; drug effects ; Lumbosacral Region ; innervation ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; therapy ; Substance P ; metabolism ; Vasoactive Intestinal Peptide ; metabolism

OBJECTIVETo compare the differences in the clinical efficacy on neurogenic bladder after spinal cord injury (SCD between the matrix needling technique combined with rehabilitation training and rehabilitation training in the patients.

METHODSSixty patients of SCI neurogenic bladder were randomized into an observation group (29 cases) and a control group (31 cases). In the control group, the conventional rehabilitation therapy, the intermittent catheterization and bladder function training were adopted, once every day, for 4 weeks totally. In the observation group, on the basic treatment of the rehabilitation as the control group, the matrix needling technique and acupuncture at sanyin points were applied. The treatment of 8 days made one session, at the interval of 2 days, continuously for 3 sessions, meaning 4 weeks totally. The bladder function score, residual urine volume and bladder capacity were compared before and after treatment in the two groups.

RESULTSThe bladder function score was reduced after treatment as compared with that before treatment in either group (both P<0. 05). The score in the observation group was lower than that in the control group after treatment (P<0. 05). No matter which spinal segment was injured, the residual urine volume after treatment was reduced as compared with that before treatment and the bladder capacity was increased (P<0. 05). The residual urine volume in the observation group was less than that in the control group after treatment and the bladder capacity was more increased (P< 0. 05).

CONCLUSIONThe conventional rehabilitation program in combination with the matrix needling technique and acupuncture at sanyin points achieve the significant efficacy on SCI neurogenic bladder.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Spinal Cord Injuries ; complications ; Treatment Outcome ; Urinary Bladder ; physiopathology ; Urinary Bladder, Neurogenic ; etiology ; physiopathology ; rehabilitation ; therapy ; Urination ; Young Adult

OBJECTIVETo research the clinical application of lower cervical pedicle screw fixation procedure.

METHODSFrom September 2011 to July 2013,32 patients underwent posterior pedicle screw-rod system fixation were retrospective analyzed includinig 20 males and 12 females with an average age of 56.4 years old ranging from 21 to 78 years. Among them, 10 patients were traumatic cervical spinal injury, 9 patients were cervical spinal canal tumors, 7 cases were posterior longitudinal ligament ossification of cervical vertebrae, 6 cases were multiple segmental cervical spondylopathy. Preoperatively, X-ray, computed tomography, magnetic resonance imaging and magnetic resonance angiography of the vertebral artery were performed in all patients. After the operation and during the follow-up,X-ray and computed tomography were performed to confirm the pedicle screw position. The accuracy of the pedicle screw placement was evaluated by 4 grades classification from Lee. The spinal cord function was assessed by ASIA impairment scale for traumatic patients and JOA score for non traumatic patients.

RESULTSTotally 144 pedicle screws performed on 32 patients from C3 to C7 involving 132 screws of grade 0,5 screws of grade 1,5 of screws grade 2 and 2 screws of grade 3 according to postoperative CT. There were 12 screws penetrating the pedicle cortex including 8 screws at lateral,2 screws at caudal, 1 screw at medial and 1 screw at cranial. The follow-up time was 12 to 33 months with an average of (21.0±1.5) months. The spinal cord function was not improved in 6 complete cervical spinal cord injury patients,but their paraplegic level descended 1 to 3 segments. Four incomplete cervical spinal cord injury patients' ASIA impairment scale was increased by 1 to 2 grades in average. The JOA score of 22 atraumatic patients increased from preoperative 11.5±0.8 to 15.9±0.6 of postoperative at 6 months (P<0.01). There were no screw loosening,screw pullout and screw-rod breakage.

CONCLUSIONThe lower cervical pedicle screw fixation can provide excellent 3D stability of the vertebral column. The operation risk and Complication could be minimized by adequate preoperative evaluation for appropriate cases and individual pedicle screw placement. It deserved the clinical expansion.

Adult ; Aged ; Cervical Vertebrae ; injuries ; surgery ; Female ; Humans ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Spinal Cord Injuries ; physiopathology ; surgery

OBJECTIVETo investigate the effect of suppressing apoptosis signal regulating kinase 1 (ASK1) on glial fibrillary acidic protein (GFAP) and vimentin expressions at the injury site and on hindlimb mobility in rats after spinal cord injury (SCI).

METHODSThe rat models of SCI were established by extradural compression of the spinal cord using an aneurysm clip. The injured rats were treated with normal saline (model group), ASK1 specific inhibitor thioredoxin (Trx group), or ASK1 monoclonal antibody (Anti-ASK1 group), and the rats receiving a sham operation underwent laminectomy without SCI. The expression of GFAP and vimentin were detected by Western blotting and immunofluorescence assay at 1, 7, 14 and 28 days after SCI. The motion function of the hindlimbs of the injured rats was assessed with Basso Beattie Bresnahan (BBB) scores, and somatosensory-evoked potentials (SEP) and motor-evoked potentials (MEP) were determined to examine the electrophysiological changes.

RESULTSAt 1 day after SCI, the expressions of GFAP and vimentin showed no significant differences among the groups; at 7, 14 and 28 days after SCI, GFAP and vimentin expressions significantly increased in Trx and Anti-ASK1 groups compared with those in the model group (P<0.01). The BBB scores showed no significant differences among the groups at 1, 7 and 14 days after SCI, while at 28 days, the BBB scores in Trx and Anti-ASK1 groups were significantly higher than those in the model group (P<0.01). At 28 days after SCI, the latent period of SEP and MEP decreased and the amplitude increased significantly in Trx and Anti-ASK1 groups compared with that in the model group (P<0.01).

CONCLUSIONBlocking ASK1 can inhibit the expression of GFAP and vimentin in glial scars and improve the outcomes of hindlimb mobility in rats after SCI.

Animals ; Disease Models, Animal ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Glial Fibrillary Acidic Protein ; metabolism ; Hindlimb ; physiopathology ; MAP Kinase Kinase Kinase 5 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism ; Vimentin ; metabolism

The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spasticity following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in Sprague-Dawley rats. Five groups were set up: normal control group, SCI-7 day (7D) model group, SCI-14D model group, SCI-7D rTMS group and SCI-14D rTMS group (n=10 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS at 8th day and 15th day after SCI respectively. Motor recovery and spasticity alleviation were evaluated by BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of GABA receptors using Western blotting and polymerase chain reaction (PCR) technique. The results showed that the BBB scores after treatment were significantly higher in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). The GABA receptors were down-regulated more significantly in SCI-14D model group than in SCI-7D model group (P<0.05). At different time points, rTMS treatment could affect the up-regulation of GABA receptors: The up-regulation of GABA receptors was more obvious in SCI-7D rTMS group than in SCI-14D rTMS treatment group (P<0.05). It was concluded that 10-Hz rTMS could alleviate spasticity following SCI and promote the motor recovery in rats, which might be attributed to the up-regulation of GABA receptors. It was also suggested that early high-frequency rTMS treatment after SCI may achieve more satisfactory curative effectiveness.
Animals ; Blotting, Western ; Male ; Muscle Spasticity ; physiopathology ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA ; physiology ; Spinal Cord Injuries ; physiopathology ; Transcranial Magnetic Stimulation

PURPOSE: The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.
Animals ; Disease Models, Animal ; Hyperalgesia ; Ligation ; Male ; Neuralgia/*metabolism/physiopathology ; Neurons/metabolism ; Nociceptors ; Pain/metabolism/*physiopathology ; Potassium Channels/*metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Spinal Cord Dorsal Horn/*metabolism ; Spinal Nerves/*injuries

OBJECTIVETo explore the effects of early intervention of acupuncture on urinary function reconstruction of neurogenic bladder after spinal cord injury, so as to find the optimal treatment timing of acupuncture.

METHODSFifty-three patients of neurogenic bladder after spinal cord injury were randomly divided into a prior-to-catheter group (25 cases) and a posterior-to-catheter group (28 cases). For the prior-to-catheter group, one week before the removal of catheter, acupoints on the abdomen and back such as Guanyuan (CV 4), Zhongji (CV 3), Baliao (Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33), Xialiao (BL 34), Jiaji (EX-B 2) and acupoints at distal end such as Zusanli (ST 36) and Sanyinjiao (SP 6) were selected; after the catheter removal, simple method. of water column was used to measure bladder capacity pressure to classify the type of bladder, and then different acupuncture manipulations were given; intermittent catheterization was performed if condition was allowed. The posterior-to-catheter group applied identical treatment after removal of catheter as the prior-to-catheter group. The treatment was given 5 times per week; after one-month treatment, five aspects including the time of first effective urination, time of establishing reflex urination, average residual volume of urine, time of residual urine less than 100 mL and quality of life (QOL) were evaluated.

RESULTSAfter treatment, the time of first effective urination, time of establishing reflex urination, average residual volume of urine and time of residual urineless than 100 mL in the prior-to-catheter group were all superior to those in the posterior-to-catheter group (all P<0. 05) ; the score of QOL was improved in two groups after treatment (both P<0. 01), but the difference between two groups was not statistically significant (P>0. 05); each index of urination function was not significant among patients with different injured segments of spinal cord (all P>0. 05).

CONCLUSIONThe early intervention of acupuncture (prior to catheter) has obvious improving function on establishing balanced bladder in patients with neurogenic bladder after spinal cord injury, which is superior to acupuncture intervention after removal of catheter, however, the effects of different injured segments on establishing balanced bladder are not different.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Spinal Cord Injuries ; complications ; Treatment Outcome ; Urinary Bladder ; physiopathology ; Urinary Bladder, Neurogenic ; etiology ; physiopathology ; therapy ; Urination ; Young Adult