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

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

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

Chronic spinal cord lesions (CSCL) which result in irreversible neurologic deficits remain one of the most devastating clinical problems. Its pathophysiological mechanism has not been fully clarified. As a crucial factor in the outcomes following traumatic spinal cord injury (SCI), the blood-spinal cord barrier (BSCB) disruption is considered as an important pathogenic factor contributing to the neurologic impairment in SCI. Vascular endothelial growth factor (VEGF) is a multirole element in the spinal cord vascular event. On one hand, VEGF administrations can result in rise of BSCB permeability in acute or sub-acute periods and even last for chronic process. On the other hand, VEGF is regarded to be correlated with angiogenesis, neurogenesis and improvement of locomotor ability. Hypoxia inducible factor-1 (HIF-1) is a primary regulator of VEGF during hypoxic conditions. Therefore, hypoxia-mediated up-regulation of VEGF may play multiple roles in the BSCB disruption and react on functional restoration of CSCL. The purpose of this article is to further explore the relationship among HIF-1, hypoxia-mediated VEGF and BSCB dysfunction, and investigate the roles of these elements on CSCL.
Animals ; Chronic Disease ; Humans ; Hypoxia-Inducible Factor 1 ; physiology ; Neovascularization, Physiologic ; Neurogenesis ; Spinal Cord ; physiopathology ; Spinal Cord Injuries ; physiopathology ; Vascular Endothelial Growth Factor A ; physiology

OBJECTIVETo observe the clinical efficacy differences between regular acupuncture combined with acupuncture at trigone of urinary bladder and simple regular acupuncture for treatment of urination dysfunction induced by spinal cord injury.

METHODSSixty patients were randomized into an observation group and a control group, 30 cases in each one. The control group was treated with regular acupuncture at Sanyinjiao (SP 6), Zusanli (ST 36), Zhongwan (CV 12) and Tianshu (ST 25), etc. Based on the treatment of control group, the observation group was additionally treated with intensive needling at trigone of urinary bladder, once a day, 30 min per treatment. Ten treatments were considered as one course, and there was an interval of two days between courses, 4 courses of treatment were given in two groups. The improvement of urination function in two groups was evaluated, and the efficacy of urination function in two groups was compared.

RESULTSAfter treatment, the times of urine leakage, maximum urine output, bladder capacity and residual urine were all improved in two groups (all P<0.05). The improvement of times of urine leakage, bladder capacity and residual urine in the observation group was superior to that in the control group (all P<0.05). The total effective rate was 96.7% (29/30) in the observation group, which was superior to 83.3% (25/30) in the control group (P<0.05).

CONCLUSIONThe efficacy of regular acupuncture combined with intensive needling at trigone of urinary bladder on urination dysfunction induced by spinal cord injury is significantly superior to that of simple regular acupuncture.

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

OBJECTIVETo evaluate the clinical efficacy of electroacupuncture (EA) combined with transperineal injection of botulinum toxin-A (BTX-A) on neurogenic bladder caused by spinal cord injury.

METHODSOne day af ter surgery, 35 cases of spinal cord injury accompanied with neurogenic bladder were randomly divided into a BTX-A plus EA group (20 cases, group A) and a BTX-A group (15 cases, group B). The two groups were both treated with regular rehabilitation training of bladder function and injection of 200 IU (4 ml) BTX-A through perineum external urethral sphincter; the group A was additionally treated with EA at Zhongji (CV 3), Guanyuan (CV 4), Shenshu (3BL 23), Huiyang (BL 35) and Baliao (Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33), Xialiao (BL 34)), once a day, 40 min per treatment. The treatment was given 6 times per week for 4 weeks. The urination status in two groups before and after treatment was observed, and urodynamics examination and urethral pressure test were also made.

RESULTSAfter 4-week treatment, mean times of urinary incontinence, mean urethral catheter output, pressure of bladder and volume of urinary incontinence were all improved in two groups (all P<0.05), which were more significant in the group A (all P<0.05). The residual urine, maximum bladder capacity, maximum urethral closure pressure and maximum urine flow rate were all improved in two groups after treatment (all P<0.01); the improvement of residual urine, maximum bladder capacity, maximum urethral closure pressure in the group A was more significant than that in the group B (all P<0.05).

CONCLUSIONElectroacupuncture com bined with transperineal injection of BTX-A could effectively improve the urination dysfunction in patients with neurogenic bladder after spinal cord injury.

Adolescent ; Adult ; Botulinum Toxins, Type A ; administration & dosage ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Injections ; Male ; Middle Aged ; Spinal Cord Injuries ; complications ; Treatment Outcome ; Urinary Bladder, Neurogenic ; drug therapy ; etiology ; physiopathology ; therapy ; Urination ; Young Adult

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

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 effect of electro-acupuncture to improve the bladder function after acute spinal cord injury in rats and its possible mechanism.

METHODSSixty healthy adult male SD rats of SPF grade, with body weight of 220 to 250 g, one week after feeding adaptation, were randomly divided into sham operation group, model group, electro-acupuncture group, electro-acupuncture control group with 15 rats in each group. Sham operation group underwent no stimulation, and the moderate damage model of spinal cord injury were made in other three groups according to modified Allens method. The model group were not treated, electro-acupuncture group were treated with electro-acupuncture on Zhibianxue and Shuidaoxue, and electro-acupuncture control group were treated with electro-acupuncture on 0.5 inch next to Zhibianxue and Shuidaoxue. The frequency of 2/100 Hz, current of 1 mA, stimulation time of 15 min, once a day, left and right alternately stimulate every time, for a total of 7 times. The changes of residual urine volume and urine output in rats at the 1st and the 7th days after operation were observed. And 7 d later, the rats were sacrificed and the injured spinal cord were taken out to observe the apoptosis, and to detect the changes of Bcl-2, Bax, Bad content.

RESULTSAfter modeling,the rats of three groups showed different bladder dysfunction. In electro-acupuncture group and electro-acupuncture control group, the residual urine volume of the 7th day after operation was significant lower than the 1st day after operation (P < 0.001), and there was statistically significant difference on the 7th day after operation between two groups (P < 0.001). Compared with model group, the urine output of electro-acupuncture group and electro-acupuncture control group was significantly increased on the 7th day after operation, and there was sig- nificant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.001). Electro-acupuncture can inhibit apoptosis of spinal cord neurons by TUNEL detection. Postoperative at 7 d, the rate of nerve cell apoptosis in electro -acupuncture group and electro-acupuncture control group was significant increased than model group (P < 0.01, P < 0.05), and there was significant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.005). Compared with model group, the positive expression rate of Bax, Bad decreased (P < 0.01, P < 0.05), and Bcl-2 increased (P < 0.01) in electro-acupuncture group and electro-acupuncture control group,there was significant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.01).

CONCLUSIONElectro-acupuncture can obviously promote the repair of acute spinal cord injury,its mechanism may be through increasing Bcl-2, inhibiting the expression of Bax, Bad, which inhibits the apoptosis of spinal cord neurons.

Animals ; Apoptosis ; Electroacupuncture ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Neurons ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; pathology ; physiopathology ; therapy ; Urinary Bladder ; physiopathology