Effects of motor imagery training after chronic,complete spinal cord injury

Abnormalities in brain motor system function are present following spinal cord injury (SCI) and could reduce effectiveness of restorative interventions. Motor imagery training, which can improve motor behavior and modulate brain function, might address this concern but has not been examined in subjects with SCI. Ten subjects with SCI and complete tetra-/paraplegia plus ten healthy controls underwent assessment before and after 7 days of motor imagery training to tongue and to foot. Motor imagery training significantly improved the behavioral outcome measure, speed of movement, in non-paralyzed muscles. Training was also associated with increased fMRI activation in left putamen, an area associated with motor learning, during attempted right foot movement in both groups, despite foot movements being present in controls and absent in subjects with SCI. This fMRI change was absent in a second healthy control group serially imaged without training. In subjects with SCI, training exaggerated, rather than normalized, baseline derangement of left globus pallidus activation. The current study found that motor imagery training improves motor performance and alters brain function in subjects with complete SCI despite lack of voluntary motor control and peripheral feedback. These effects of motor imagery training on brain function have not been previously described in a neurologically impaired population, and were similar to those found in healthy controls. Motor imagery might be of value as one component of a restorative intervention.     

c-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice

C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In Jnk1^−/− and Jnk3^−/− mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.     

Metallothionein-II improves motor function recovery and increases spared tissue after spinal cord injury in rats

After spinal cord injury (SCI), a complex cascade of pathophysiological processes rapidly damages the nervous tissue. The initial damage spreads to the surrounding tissue by different mechanisms, including oxidative stress. We have recently reported that the induction of metallothionein (MT) protein is an endogenous rapid-response mechanism after SCI. Since the participation of MT in neuroprotective processes after SCI is still unknown, the aim of the present study was to evaluate the possible neuroprotective effect of exogenously administered MT-II during the acute phase after SCI in rats. Female Wistar rats weighing 200-250g were submitted to spinal cord contusion by means of a computer-controlled device (NYU impactor). Rats received several doses of MT-II (3.2, 10 and 100μg) at 2 and 8h after SCI. Results of the BBB scale were statistically analysed using an ANOVA of repeated-measures, followed by Tukey's test. Among the three doses tested, only 10 and 100μg were able to significantly increase (p<0.05) BBB scale scores eight weeks after SCI from a mean of 7.88 in the control group, to means of 12.63 and 10.88 for the 10 and 100μg doses of MT-II, respectively. The amount of spared tissue was also higher in the groups treated with 10 and 100μg, as compared to the control group values. Results from the present study demonstrate a significant neuroprotective effect of exogenously administered MT-II. Further studies are needed in order to characterize the mechanisms involved in this neuroprotective action.     

Effect of cervical spinal cord hemisection on the expression of axon growth markers

To evaluate the plasticity processes occurring in the spared and injured tissue after partial spinal cord injury, we have compared the level of axon growth markers after a C2 cervical hemisection in rats between the contralateral (spared) and ipsilateral (injured) cervical cord using western blotting and immunohistochemical techniques. In the ipsilateral spinal cord 7 days after injury, although GAP-43 levels were increased in the ventral horn caudal to the injury, they were globally decreased in the whole structure (C1–C6). By contrast, in the contralateral intact side 7 days and 1 month after injury, we have found an increase of GAP-43 and βIII tubulin levels, suggesting that processes of axonal sprouting may occur in the spinal region contralateral to the injury. This increase of GAP-43 in the contralateral spinal cord after cervical hemisection may account, at least partially, to the spontaneous ipsilateral recovery observed after a cervical hemisection.     

Interlimb reflexes following cervical spinal cord injury in man

Summary The reflex interconnection of lower and upper extremity muscles was investigated in subjects with chronic (> 1 year post-injury) lesions to the cervical spinal cord. Lower extremity mixed nerves were stimulated with single shocks or with brief trains of high-frequency stimuli of varying intensities. EMG from a number of lower and upper extremity muscles was recorded on magnetic tape for later analysis. In one population of spinal cord injury (SCI) subjects, single stimuli to lower extremity nerves resulted in muscle responses in both ipsi- and contralateral upper extremity muscles. The minimal response latency to a single shock was typically much less in muscles on the ipsilateral side than for contralateral upper extremity muscles. Application of brief trains of stimuli (for example, 2 stimulus pulses at 500 Hz) typically resulted in a large reduction in latency to the contralateral motor response, such that it was now approximately equal to the ipsilateral motor response latency. This decline in response latency was not gradual with increasing afferent input. Instead, the response occurred either early or late, but not at intermediate latencies. Stimuli which were subthreshold for evoking M-waves or H-reflexes were sometimes still adequate to evoke upper extremity motor responses. Once the threshold had been exceeded, the magnitude of the evoked response appeared to be independent of the stimulus magnitude. These reflex interconnections of lower and upper extremities were obtained only from subjects with chronic and motor-complete cervical spinal cord injury. No such interlimb responses were seen in control subjects, or in subjects who had recovered some motor function below the level of their injury, and were now considered to be motor-incomplete quadriplegics.     

The intralimb coordination of the flexor reflex response is altered in chronic human spinal cord injury

The current study compared the intralimb coordination of flexor reflex responses in spinal intact and complete chronic spinal cord injured (SCI) individuals. Noxious electrocutaneous stimulation was applied at the apex of the medial arch of the foot (50 mA, 500 Hz, 1 ms pulse width, 20 ms) in 21 complete chronic SCI and 19 spinal intact volunteers and the flexor reflex response was quantified by measuring the isometric joint torques at the ankle, knee and hip. The results showed that SCI individuals had significantly smaller peak knee and hip joint flexion torques, often exhibited a net knee extension torque, and produced a much smaller hip joint flexion torque during the flexor reflex response in contrast to the spinal intact individuals. The latency of the reflex response, measured from the tibialis anterior electromyogram, was comparable in both test populations. These findings indicate that the intralimb coordination of the flexor reflex response of chronic complete SCI individuals is altered, possibly reflecting a functional reorganization of the flexion pathways of the spinal cord.     

Atorvastatin prevents early apoptosis after thoracic spinal cord contusion injury and promotes locomotion recovery

The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5 mg/kg) at 2 h after the contusion injury; (2) physiological saline at 2 h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p < 0.05) improvement in locomotion at week 4 post-SCI compared to vehicle-treated animals. Explaining this outcome, caspase-3 activity decreased by 50% (p < 0.05), and the histological TUNEL method revealed a decrease of approximately 20% in apoptotic cells at the injury site (p < 0.01) at 4 h post-SCI in atorvastatin-treated rats in comparison to vehicle-treated controls. These data demonstrate that atorvastatin is effective after experimental spinal cord contusion injury in preventing early apoptosis at the injury site within 2 h post-administration.     

脊髓挫伤速度对颈脊髓原发性损伤影响的实验研究

目的　确定脊髓挫伤速度是脊髓损伤的因素,探讨不同速度的脊髓挫伤对大鼠颈脊髓原发性损伤的影响。  方法    20只成年雄性Sprague-Dawley大鼠随机分为快速组（500 mm/s,n=8）、慢速组（5 mm/s,n=8）和对照组（n=4）。用直径为4 mm的平头圆锥打击头在C5水平产生1.5 mm的挫伤位移。损伤后即行心脏固定,切取以挫伤部位为中心长约1.5 cm的脊髓组织。行连续矢状位冰冻切片。HE染色观察脊髓大体形态,计算出血量。β-APP免疫组化后观察轴索损伤程度。  结果　挫伤后观察到脊髓表面有一带状出血,且快速组出血带颜色更深。快速组挫伤位移为(1.50±0.05) mm,最大力为(5.3±1.2) N;慢速组挫伤位移为(1.51±0.04) mm,最大力为(2.8±0.6) N,两组间最大力的差异有显著性（P=0.001）。HE染色显示脊髓出血大部分都集中在灰质,白质相对较少。快速组脊髓总出血量、灰质出血量和白质出血量分别为0.94、0.71和0.23 mm3,慢速组分别为0.55、0.43和0.12 mm3,其中两组间总出血量和灰质出血量的差异有显著性（P＜0.05）。β-APP免疫组化观察到快速组轴索断裂比慢速组更为严重。  结论　脊髓挫伤速度是影响脊髓原发性损伤的因素,快速的脊髓挫伤导致的原发性脊髓损伤更为严重,导致更多的脊髓出血和轴索断裂。     

A型肉毒杆菌神经毒素重链干预大鼠脊髓损伤后蛋白表达的初步研究

目的:初步观察大鼠脊髓损伤模型基础上局部注射小剂量A型肉毒杆菌神经毒素重链(BoNT/A HC)后对局部蛋白表达谱的影响,为探讨BoNT/A HC干预在体神经损伤后相关蛋白表达及其干预神经再生机制提供实验基础。方法:复制大鼠单侧腰段脊髓损伤模型;采用SDS-PAGE及双向电泳观察不同剂量BoNT/A HC(2μg、4μg、6μg和8μg)对脊髓损伤后局部(包括损伤部位及其近头端部分脊髓组织)蛋白表达谱的干预作用。结果:大鼠单侧腰段脊髓损伤2 d时局部脊髓组织结构明显破坏崩解,损伤波及左侧脊髓灰质及白质;脊髓损伤局部SDS-PAGE及考马斯亮蓝染色显示,于损伤同时局部一次性注射不同剂量BoNT/A HC后,某些蛋白表达与单纯损伤组相比明显不同,而与正常组基本一致;双向电泳结果进一步显示,损伤局部注射6μg BoNT/A HC后2 d和20 d时,在不同等电点及不同蛋白分子量水平上,有10余种蛋白表达与单纯损伤组明显不同,呈向正常转化的趋势。结论:大鼠脊髓损伤局部注射BoNT/A HC一定时间可影响损伤局部蛋白表达谱的变化,这种变化呈现由损伤造成的蛋白表达变化被转向正常的趋势。     

脐带间充质干细胞治疗脊髓损伤临床分析

目的观察脐带间充质干细胞（UC-MSCs）鞘内注射治疗脊髓损伤（SCI）的临床效果及安全性。方法对2008年1月至2010年10月收治的22例SCI患者,给予UC—MSCs鞘内注射治疗,细胞数1×10^6个／（kg·次）,1次／周,4次为1个疗程,其中4例接受2个疗程,1例接受3个疗程,余均接受1个疗程。采用美国脊髓损伤协会制定的脊髓损伤神经功能评分标准（ASIA标准）对患者治疗前后神经功能进行评定,采用国际神经修复学会脊髓损伤功能评价量表（IANR—SCIRFS）对患者治疗前后日常生活活动能力进行评定。结果22例患者中13例有效,9例无效。不完全性SCI患者有效率达81．25％,完全性SCI的6例患者均无效。有5例有效的患者接受了2～3个疗程治疗,疗效均有进一步的提高。有效患者多表现为运动和／或感觉功能改善,大小便控制能力增强。22例患者治疗后1个月与治疗前比较,痛觉、触觉、运动、日常生活活动能力评分均有明显升高（P〈0．01）。治疗后常见的不良反应有头痛（1例）、腰痛（1例）,均在1～3d内消失。随访3个月至3年,无治疗相关不良事件发生。结论UC—MSCs鞘内注射治疗是安全的,可以改善大部分不完全性SCI患者的神经功能,提高这些患者的生活质量。     

小鼠颈脊髓半侧挫伤模型的建立及其组织学特点

目的　建立基于位移控制的C57/6J小鼠C5脊髓半侧挫伤模型,观察其脊髓组织学改变。 方法　C57BL/6小鼠在麻醉状态下行C5左侧椎板切除术,打击头（直径0.75 mm）对准C5左侧,由电磁伺服材料试验机驱动挫伤脊髓,设定打击位移0.9 mm,打击速度50 mm/s。损伤后1周脊髓标本取材,EC染色,作组织学定量分析。 结果　打击参数结果稳定性与重复性良好。打击位移、打击速度和打击力分别为（0.880±0.035）mm、（48.146±4.367）mm/s、（0.407±0.129）N,损伤中心的脊髓组织学表现为：伤侧脊髓有明显的出血及正常组织结构破坏,脊髓背侧束、脊髓后角和部分前角有破坏;健侧脊髓结构基本保持完整。计算损伤中心平面的残存灰质比例、残存白质比例及损伤面积比例分别为（19±7）%、（88±9）%及（28±4）%。 结论　本研究成功建立小鼠颈脊髓半侧挫伤模型,此模型具有重复性较好的力学参数,表现出典型的单侧颈脊髓损伤的组织学特征,可为脊髓损伤分子机制和治疗研究奠定基础。     

Simvastatin treatment improves functional recovery after experimental spinal cord injury by upregulating the expression of BDNF and GDNF

The aim of this study was to determine the therapeutic efficacy of simvastatin treatment starting 1 day after spinal cord injury (SCI) in rat and to investigate the underlying mechanism. Spinal cord injury was induced in adult female Sprague–Dawley rats after laminectomy at T9-T10. Then additionally with sham group (laminectomy only) the SCI animals were randomly divided into 3 groups: vehicle-treated group; 5-mg/kg simvastatin-treated group; and 10-mg/kg simvastatin-treated group. Simvastatin or vehicle was administered orally at 1 day after SCI and then daily for 5 weeks. Locomotor functional recovery was assessed during 8 weeks postoperation by performing open-field locomotor test and inclined-plane test. At the end of study, motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were assessed to evaluate the integrity of spinal cord pathways. Then, the animals were killed, and 1-cm segments of spinal cord encompassing the injury site were removed for histopathological analysis. Immunohistochemistry was performed to observe the expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) in the spinal cord. Results show that the simvastatin-treated animals showed significantly better locomotor function recovery, better electrophysiological outcome, less myelin loss, and higher expression of BDNF and GDNF. These findings suggest that simvastatin treatment starting 1 day after SCI can significantly improve locomotor recovery, and this neuroprotective effect may be related to the upregulation of BDNF and GDNF. Therefore, simvastatin may be useful as a promising therapeutic agent for SCI.     

Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation

We provide evidence that the human spinal cord is able to respond to external afferent input and to generate a sustained extension of the lower extremities when isolated from brain control. The present study demonstrates that sustained, nonpatterned electrical stimulation of the lumbosacral cord—applied at a frequency in the range of 5–15 Hz and a strength above the thresholds for twitches in the thigh and leg muscles—can initiate and retain lower-limb extension in paraplegic subjects with a long history of complete spinal cord injury. We hypothesize that the induced extension is due to tonic input applied by the epidural stimulation to primary sensory afferents. The induced volleys elicit muscle twitches (posterior root muscle-reflex responses) at short and constant latency times and coactivate the configuration of the lumbosacral interneuronal network, presumably via collaterals of the primary sensory neurons and their connectivity with this network. We speculate that the volleys induced externally to the lumbosacral network at a frequency of 5–15 Hz initiate and retain an extension pattern generator organization. Once established, this organization would recruit a larger population of motor units in the hip and ankle extensor muscles as compared to the flexors, resulting in an extension movement of the lower limbs. In the electromyograms of the lower-limb muscle groups, such activity is reflected as a characteristic spatiotemporal pattern of compound motor-unit potentials.Abbreviations C Cervical - CMUP Compound motor-unit potential - EMG Potential - CNS Central nervous system - EMG Electromyography, electromyographic - H Hamstring - L Lumbar - MLR Mesencephalic locomotor region - PARA Paraspinal muscles - Q Quadriceps - S Sacral - SCI Spinal cord injury, spinal cord-injured - SCS Spinal cord stimulation - T Thoracic - TA Tibialis anterior - TS Triceps surae     

护理干预对大鼠脊髓损伤后运动功能修复的影响

目的探索护理干预对脊髓损伤大鼠运动功能恢复程度的影响。方法将60只大鼠随机分为A、B、C共3个组(每组20只),A组为正常对照组,B组为实验对照组,C组为实验组;B组给予常规护理,C组在给予常规护理的基础上给予肌肉按压、关节被动运动、皮肤护理等护理干预。应用BBB评分和斜坡试验评价大鼠脊髓损伤后不同时相点的行为学变化,采用多道生理信号采集系统和电子天平称量,观察大鼠腓肠肌在脊髓损伤后不同时间点肌电反应和肌湿重变化。结果 BBB评分和斜坡试验结果基本一致,C组与B组相比,C组大鼠后肢功能明显改善,但与A组(正常对照组)相比,其后肢功能评分相差很大;腓肠肌肌电反应纤颤电位波幅C组较B组高;腓肠肌湿重下降C组较B组减轻。结论护理干预可延缓肌肉萎缩速度、改善运动功能,促进损伤脊髓功能的部分运动功能恢复。     

Enhanced functional recovery from spinal cord injury following intrathecal or intramuscular administration of poliovirus replicons encoding IL-10

Poliovirus-based vectors (replicons) have been shown to maintain the in vitro tropism of poliovirus for motor neurons of the CNS. To determine if replicons could be effective for delivery of potentially beneficial proteins to the CNS, we have constructed and characterized a replicon encoding IL-10. IL-10 was rapidly produced in tissue culture cells following in vitro infection with replicons encoding IL-10. Intrathecal inoculation of replicons encoding IL-10 into the non-injured CNS of mice transgenic for the poliovirus receptor resulted in expression of IL-10 within motor neurons at 24-48 h post-inoculation, which subsided by 72-96 h post-inoculation. Single intrathecal or intramuscular injections of replicons were given following spinal cord trauma. Animals receiving replicons encoding IL-10 demonstrated a greater functional recovery in the first 24 h after injury that was maintained throughout the testing period. Compared to animals given replicons encoding gfp, CNS tissue from animals given replicons encoding IL-10 revealed extensive expression of IL-10 from astrocytes around the CNS lesion during the first week following injury. The expression of IL-10 from astrocytes also correlated with more resting microglia as opposed to the rounded activated microglia seen in animals given replicons encoding gfp. Results of these studies establish that replicons can be used to express biologically active molecules in motor neurons of the CNS and these biologically active molecules can have a direct effect on the CNS or induce a cascade of molecules that can influence the cellular composition and activation state of cells within the CNS.     

Long-term spinal cord injury increases susceptibility to isometric contraction-induced muscle injury

Complete spinal cord injury (SCI) results in inactivation and unloading of affected skeletal muscles. Unloading causes an increased susceptibility of muscle to contraction-induced injury. This study used magnetic resonance imaging (MRI) to test the hypothesis that isometric contractions would evoke greater muscle damage to the quadriceps femoris muscle (mQF) of SCI subjects than that of able-bodied (AB) controls. MR images were taken of the mQF prior to, immediately post, and 3 days post electromyostimulation (EMS). EMS consisted of five sets of ten isometric contractions (2 s on/6 s off, 1 min between sets) followed by another three sets of ten isometric contractions (1 s on/1 s off, 30 s between sets). Average muscle cross-sectional area (CSA) and the relative areas of stimulated and injured muscle were obtained from MR images by quantifying the number of pixels with an elevated T2 signal. SCI subjects had significantly greater relative area [90 (2)% versus 66 (4)%, P<0.05; mean (SE)] but a lesser absolute area [16 (3) cm² versus 44 (6) cm², P<0.05] of mQF stimulated than AB controls. During EMS, peak torque was reduced by 66% and 37% for SCI and control subjects, respectively. Three days post EMS, there was a greater relative area of stimulated mQF injured for the SCI subjects [25 (6)% versus 2 (1)%, P<0.05]. Peak torque remained decreased by 22% on day 3 in the SCI group only. These results indicate that affected muscle years after SCI is more susceptible to contraction-induced muscle damage, as determined by MRI, compared to AB controls. They also support the contention that electrically elicited isometric contractions are sufficient to cause muscle damage after a prolonged period of inactivity.     

Complete spinal cord transection at different postnatal ages: recovery of motor coordination correlated with spinal cord catecholamines

Summary The ability of rats that are cordotomized at different times between postnatal day (PN) 0-28, to recover four-limb motor coordination, varies as a function of the time of cordotomy. The rats were evaluated at 37 independent observers for four-limb coordination, scored on a scale of 10 (best) to 0 (worst). The rank order of recovery from best to worst is: PN7>PNO>PN14> PN21>PN28. The hindlimbs are active only when they receive proprioceptive sensation from contact with a surface. They appear completely paralyzed when, for example, the rats are challenged to climb an inclined surface of spaced metal bars (Fig. 4). The content of both dopamine (DA) and norepinephrine (NE) in the adult spinal cord rostral to the transection, also varied as a function of transection time. DA was present in the lumbar (that is, caudal to the transection) region of the cord in the PNO, PN7 and PN14 groups, with the highest concentration in the PN7 group. NE was not present in the lumbar region in any of the experimental groups. It is concluded that rats can recover a substantial degree of four limb motor activity after cordotomy, provided the cord is transected before the fourteenth postnatal day. Moreover, this recovery of motor coordination, apparently correlates closely with the presence of DA in the lumbar region of the cord. Whether there is a causal relationships between recovery of motor coordination and the content of DA in the lumbar cord is not known.     

Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway

Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30 min after the SCI was successfully induced, the animals were intraperitoneally given 40 mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin–eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin – 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.     

A self-assembling peptide reduces glial scarring,attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury

The pathophysiology of spinal cord injury (SCI) involves post-traumatic inflammation and glial scarring which interfere with repair and recovery. Self-assembling peptides (SAPs) are molecules designed for tissue engineering. Here, we tested the performance of K₂(QL)₆K₂ (QL6), a SAP that attenuates inflammation and glial scarring, and facilitates functional recovery. We injected QL6 into the spinal cord tissue of rats 24 h after clip compression SCI. QL6 led to a significant reduction in post-traumatic apoptosis, inflammation and astrogliosis. It also resulted in significant tissue preservation as determined by quantitative histomorphometry. Furthermore, QL6 promoted axonal preservation/regeneration, demonstrated by BDA anterograde and Fluorogold retrograde tracing. In vitro experiments found that a QL6 scaffold enhanced neuronal differentiation and suppressed astrocytic development. The electrophysiology confirmed that QL6 led to significant functional improvement of axons, including increased conduction velocity, reduced refractoriness and enhanced high-frequency conduction. These neuroanatomical and electrophysiological improvements were associated with significant neurobehavioral recovery as assessed by the Basso–Beattie–Bresnahan technique. As the first detailed examination of the pathophysiological properties of QL6 in SCI, this work reveals the therapeutic potential of SAPs, and may suggest an approach for the reconstruction of the injured spinal cord.     

兔颈脊髓半侧挫伤模型的建立及其MRI和组织学表现的研究

目的 建立兔颈脊髓半侧挫伤模型,观察不同程度损伤24小时后其MRI及组织学表现。方法 22只成年雄性新西兰兔,随机分为中度损伤组（n=9）、重度损伤组（n=9）和假手术组（n=4）。直径为3.0 mm的打击头由电磁伺服材料试验机驱动,对准C5脊髓左侧行高速挫伤（500 mm/s）。根据打击头的位移距离分为位移2.0 mm组（中度损伤组）和位移2.8 mm组(重度损伤组)。假手术组仅暴露C5脊髓,不进行挫伤。损伤后24小时每组随机取两例行MRI影像学检查,所有动物均取材进行组织学观察,测量横断面脊髓出血面积。 结果 中度损伤组打击力和位移分别为(2.47±0.39) N和(1.99±0.02) mm,重度损伤组打击力和位移分别为(5.16±0.82) N和(2.76±0.02) mm,中度损伤组的打击力明显小于重度损伤组（P<0.05）。MRI结果显示,中度及重度损伤组均可见C5左侧脊髓信号改变。HE染色显示脊髓左侧有明显的出血及脊髓组织结构破坏,中度损伤组损伤中心横截面出血面积（0.012±0.006）mm2明显小于重度损伤组（0.039±0.006）mm2（P<0.05）。 结论 本文建立的兔颈脊髓半侧挫伤模型能够控制挫伤位移,实现对脊髓的高速打击。不同程度的颈脊髓半侧挫伤在打击力、MRI影像学及组织学上均有不同。