Effects of a metalloporphyrinic peroxynitrite decomposition catalyst,ww-85, in a mouse model of spinal cord injury

The aim of the present study was to assess the effect of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in the pathophysiology of spinal cord injury (SCI) in mice. Spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5–T8 laminectomy. SCI in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, production of inflammatory mediators, tissue damage and apoptosis. ww-85 treatment (30–300 µg/kg, i.p. 1 h after the SCI) significantly reduced in a dose-dependent manner: (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation and PARP activation, (4) pro-inflammatory cytokines expression, (5) NF-κB activation and (6) apoptosis. Moreover, ww-85 significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. The results demonstrate that ww-85 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.     

Absence of endogenous interleukin-10 enhances secondary inflammatory process after spinal cord compression injury in mice

Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 on the modulation of the secondary events in mice subjected to spinal cord injury induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy. IL-10 wild-type mice developed severe spinal cord damage characterized by oedema, tissue damage and apoptosis (measured by Annexin-V, terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Bax, Bcl-2, and Fas-L expression). Immunohistochemistry demonstrated a marked increase of localization of TNF-α, IL-1β and S100β, while western blot analysis shown an increased immunoreactivity of inducible nitric oxide synthase in the spinal cord tissues. The absence of IL-10 in IL-10 KO mice resulted in a significant augmentation of all the above described parameters. We have also demonstrated that the genetic absence of IL-10 worsened the recovery of limb function when compared with IL-10 wild-type mice group (evaluated by motor recovery score). Taken together, our results clearly demonstrate that the presence of IL-10 reduces the development of inflammation and tissue injury events associated with spinal cord trauma.     

Adiponectin-Mediated Analgesia and Anti-Inflammatory Effects in Rat

The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation.     

Early Endogenous Activation of CB1 and CB2 Receptors after Spinal Cord Injury Is a Protective Response Involved in Spontaneous Recovery

Spinal cord injury (SCI) induces a cascade of processes that may further expand the damage (secondary injury) or, alternatively, may be part of a safeguard response. Here we show that after a moderate-severe contusive SCI in rats there is a significant and very early increase in the spinal cord content of the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA). Since 2-AG and AEA act through CB1 and CB2 cannabinoid receptors, we administered at 20 minutes after lesion a single injection of their respective antagonists AM281 and AM630 alone or in combination to block the effects of this early endocannabinoid accumulation. We observed that AM281, AM630 or AM281 plus AM630 administration impairs the spontaneous motor recovery of rats according to the Basso-Beattie-Bresnahan (BBB) locomotor scale. However, blockade of CB1, CB2 or both receptors produced different effects at the histopathological level. Thus, AM630 administration results at 90 days after lesion in increased MHC-II expression by spinal cord microglia/monocytes and reduced number of serotoninergic fibres in lumbar spinal cord (below the lesion). AM281 exerted the same effects but also increased oedema volume estimated by MRI. Co-administration of AM281 and AM630 produced the effects observed with the administration of either AM281 or AM630 and also reduced white matter and myelin preservation and enhanced microgliosis in the epicentre. Overall, our results suggest that the endocannabinoids acting through CB1 and CB2 receptors are part of an early neuroprotective response triggered after SCI that is involved in the spontaneous recovery after an incomplete lesion.     

脊髓缺血再灌注损伤的防治概况

脊髓缺血-再灌注损伤(SCII)是一种严重的神经系统损伤,是缺血脊髓组织恢复血液灌注后,脊髓组织的损伤反而加重,表现为其神经损害体征和形态学改变较前更加明显,其发生机制是多因素的综合结果,治疗措施也具有多样性,脊髓缺血后脊髓微血管结构及功能的破坏和脊髓水肿等是脊髓功能损害的主要诱因,至今为止,脊髓缺血再灌注损伤的防治主要有药物及物理治疗等方法,本文作者通过查阅中外文献对脊髓缺血再灌注损伤的特征、发生机制及防治措施作一综述,希望对研究脊髓缺血再灌注损伤防治的学者能有所帮助。     

Phospholipids of normal and experimentally injured spinal cord of the miniature pig

Experimental spinal cord trauma was produced in 3-month-old SS-1 minature pigs by dropping a 25 g weight from a height of 20 cm upon the exposed spinal cord. The histological lesion consisted of edema and hemorrhage. Phospholipid concentration and composition, cholesterol concentration and phospholipid fatty acid composition were determined in whole spinal cord 3 hours after injury, and in spinal cord myelin 5 hours after injury. Three hours after injury phospholipid and cholesterol concentration were decreased by about 14% in the whole spinal cord. Trauma had no effect on the phospholipid composition of whole spinal cord and myelin. Fatty acid composition of myelin also did not change after injury, and changed very slightly in the whole spinal cord. It is concluded that edema following spinal cord trauma is much more extensive than previously assumed. Furthermore, peroxidation of membrane lipid fatty acids does not appear to be a significant factor in spinal cord pathology 3 hours after injury.     

Developmental study of the shortened spinal cord in the adult tiger puffer fish, Takifugu rubripes (Teleostei)

ABSTRACT The spinal cords of vertebrates are generally divided into the cord proper and the minute filum terminale. While the spinal cord extends the entire length of the vertebral canal in the adult tiger puffer, Takifugu rubripes, the cord proper is greatly reduced in length and almost all of the canal is occupied by the filum terminale, which is tape-like rather than thread-like. The dorsal and ventral roots of the spinal nerves extend, respectively, above and below the filum terminale; as a whole, these form a massive cauda equina. Supramedullary cells are found in the rostral half of the medulla oblongata caudal to the cerebellum. In 4-mm long tiger puffers, the spinal cord is cylindrical and supramedullary cells are found in the rostral half of the cord. In 7-mm puffers, the longitudinally arranged ventral roots appear ventrally in the middle portion of the spinal cord. In 15-mm puffers, the dorsal and ventral roots run longitudinally along the spinal cord and have noticeably increased in number. Supramedullary cells are located in the rostral 15% of the cord. In 21-mm puffers, the spinal cord in large part becomes dorsoventrally flattened. In 30-mm puffers, the spinal cord becomes much flatter, and supramedullary cells now are located mainly in the medulla oblongata. These observations indicate that formation of the shortened spinal cord proper is due to at least two developmental processes. First, the elongation of the spinal cord proper is remarkably less than that of the vertebral canal. Second, the bulk of the spinal cord proper is translocated to the cranial cavity, where it is transformed into part of the medulla oblongata.     

Brain and spinal cord interaction: protective effects of exercise prior to spinal cord injury

We have investigated the effects of a spinal cord injury on the brain and spinal cord, and whether exercise provided before the injury could organize a protective reaction across the neuroaxis. Animals were exposed to 21 days of voluntary exercise, followed by a full spinal transection (T7-T9) and sacrificed two days later. Here we show that the effects of spinal cord injury go beyond the spinal cord itself and influence the molecular substrates of synaptic plasticity and learning in the brain. The injury reduced BDNF levels in the hippocampus in conjunction with the activated forms of p-synapsin I, p-CREB and p-CaMK II, while exercise prior to injury prevented these reductions. Similar effects of the injury were observed in the lumbar enlargement region of the spinal cord, where exercise prevented the reductions in BDNF, and p-CREB. Furthermore, the response of the hippocampus to the spinal lesion appeared to be coordinated to that of the spinal cord, as evidenced by corresponding injury-related changes in BDNF levels in the brain and spinal cord. These results provide an indication for the increased vulnerability of brain centers after spinal cord injury. These findings also imply that the level of chronic activity prior to a spinal cord injury could determine the level of sensory-motor and cognitive recovery following the injury. In particular, exercise prior to the injury onset appears to foster protective mechanisms in the brain and spinal cord.     

Motor mechanisms in the turtle spinal cord

We reveal the intrinsic motor capacity of the spinal cord by examining motor behaviours produced by spinal segments caudal to a complete transection of the spinal cord. The turtle spinal cord generates three forms of the scratch reflex in the absence of neural inputs from supraspinal structures. Each form exhibits a characteristic motor neuron discharge pattern. We test the ability of the spinal cord to generate organized motor patterns in the absence of movement-related sensory feedback by examining motor neuron discharge patterns in spinal preparations that are immobilized with a neuromuscular blocking agent. The motor neuron discharge pattern associate with each form is observed in the spinal immobilized preparation. Each of these motor patterns is therefore generated centrally within the spinal cord.     

MKP-1和磷酸化ERK蛋白在急性脊髓损伤大鼠模型中表达的实验研究

探讨丝裂原活化蛋白激酶(Mitogen activated protein kinase,MAPK)相关蛋白丝裂原活化蛋白激酶磷酸酶(Mitogen activated protein kinase phoshatase-1,MKP-1)和磷酸化细胞外信号调节激酶(Extracellular sigIlal-regulated kinases,ERK)在大鼠脊髓损伤后表达的变化及其意义.20只SD大鼠随,机分为实验组及假手术对照组.实验组采用改良Allen'S打击法制作脊髓损伤动文为实验组及假手术对照组同法暴露脊髓,但不损伤脊髓.2组大鼠术后12h取手术段脊髓,用苏木精--伊红染色观察损伤脊髓组织病理变化和检测脊髓标本损伤段的MKP-1和磷酸化ERK蛋白表达的差异.实验组脊髓HE染色显示存在大量出血坏死后形成的囊腔,组织和神经细胞水肿以及神经纤维溶解消失.免疫组化和Western Blot结果发现.术后第12h实验组MKP-1蛋白的表达减少,同时磷酸化ERK-1蛋白的表达量却明显增加,差别有显著性意义(P<0.01).脊髓组织受重物打击后可下调MKP-1蛋白的表达,同时显著增加磷酸化ERK蛋白,而这可能是脊髓损伤的机制之一.     

Optical Monitoring and Detection of Spinal Cord Ischemia

Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.     

Mechanism of formation of intramedullary cavities and their role in the regeneration of the spinal cord

The spinal cord preparations of 38 dogs and 20 rabbits have been studied with the aim to investigate the influence of the cerebrospinal fluid on the spinal cord nervous tissue. The spinal cord preparations of 8 patients having trauma of the vertebral column with interruption of the spinal cord have also been studied. As demonstrate histological investigations, the cerebral tissue of the pieces, put into the flask with liquor, in the subarachnoidal space of the canine spinal cord, in diastasis between the ends of the cut spinal cord during 6 h up to 7 days, swells, becomes edematous. Cavities occupying about 30% of the area in the slices studied appear in it. At hemisection of the rabbit spinal cord without closure of the defect in the meninx vasculosa with the glue MK-6, the area of the cavity formation varies from 24 up to 35%, comparing the whole area of the preparation, while in rabbits with hemisection and successive gluing of the defect in the meninx vasculosa the area of the nervous tissue destruction makes 13-18%. It has been proved that the scar forming in the traumatized segment of the spinal cord does not present a continuous formation, but contains a large amount of cavities that prevent regeneration of nerve fibers. The experimental data concerning lysing effect of the cerebrospinal fluid on the traumatized nervous tissue are confirmed by the results obtained at investigating the preparations of the spinal cord of the patients died as the cause of the spinal cord trauma.     

三七总皂苷对脊髓损伤后BDNF 的表达及运动功能的影响

目的:探讨三七总皂苷(total panax notoginseng saponins,tPNS)对脊髓半横断损伤后对脑源性神经营养因子(Brain-derivedneurotrophic factor,BDNF)表达以及运动功能恢复的作用的影响。方法:大鼠随机分为正常组和实验组,实验组大鼠脊髓T10右侧半横断模型,损伤后15min,腹腔注射三七总皂苷,剂量为20mg.kg-1,以后每天给药一次,溶媒对照组注射等量生理盐水。术后进行BBB评分和斜板实验检测;动物分别存活1d、3d、7d、14d、28d后,采用免疫荧光化学方法检测脊髓损伤远侧端BDNF表达的变化。结果:BBB评分及斜板实验结果显示,三七总皂苷能明显促进脊髓损伤后运动功能的恢复,尤其是损伤后7d和14d,三七总皂苷组评分明显高于溶媒对照组。免疫组化结果显示:脊髓半横断损伤后,损伤远侧端损伤侧BDNF的表达强于对侧,损伤侧BDNF的表达呈现出1d,3d逐渐增强,7d达高峰的趋势,14dBDNF的表达逐渐下降,至28d仍略高于正常组。三七总皂苷组和溶媒对照组相比,BDNF表达的时间趋势相同,但相同时间点BDNF的表达强于对照组,尤其是3d、7d。结论:三七总皂苷能增强脊髓半横断损伤后BDNF的表达,这可能是其改善脊髓再生的微环境,促进脊髓损伤后运动功能恢复的机制之一。     

脊髓缺血损伤合并脓毒症后脊髓ZnT1表达的研究

目的：研究脊髓缺血损伤合并脓毒血症后大鼠脊髓的病理改变及脊髓组织中锌转运体1（zinc transporter1,ZnT1）的表达规律。方法：将32只wistar大鼠随机分为假手术组（s组,n=8）、腹主动脉阻断组（I／R组,n=8）、内毒素组（LPS组,n=8）和腹主动脉阻断＋内毒素组（I／R＋LPS组,n=8）。用HE染色的方法检测脊髓组织病理损害,用免疫组织化学的方法检测脊髓组织中ZnTl的表达规律。结果：1．病理结果改变：除S组外,I／R组、LPS组、UR＋LPS组三组大鼠HE染色切片中均可见脊髓组织损伤,各组脊髓损伤的严重程度有以下规律：S组〈I/R组〈LPS组〈I／R＋LPS组。2．免疫组化结果：脊髓损伤组ZnT1的表达较假手术组均增加（P〈0．05）。结论：1．脊髓缺血损伤合并内毒素攻击可导致严重的脊髓损伤。2．腹主动脉阻断合并内毒素攻击所致脊髓损伤早期脊髓组织中ZnT1表达上调,可能通过调节脊髓损伤早期脊髓组织中锌稳态平衡进而在脊髓损伤后脊髓神经元的病理生理活动中发挥重要作用,这一实验结果可为寻找早期脊髓损伤预防措施提供新的思路。     

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.     

Generation of electromotor neurons in Sternarchus albifrons: differences between normally growing and regenerating spinal cord

This study examines the regulation of the number of electromotor neurons during postnatal growth of the spinal cord in the gymnotiform teleost Sternarchus albifrons. It specifically asks whether a large overproduction of electromotor neurons and a wave of cell death, similar to those occurring during spinal cord regeneration in this species, play a role in the on-going growth at the caudal tip of the normal spinal cord. Neurons are produced from ependymal precursors at the caudal end of the spinal cord during both normal growth in the adult and regeneration of the spinal cord in this species. Previous studies have demonstrated that during spinal cord regeneration after amputation of the tail in Sternarchus, there is an initial massive (up to fivefold) overproduction of electromotor neurons, followed by a wave of cell death which reduces the number of these neurons to the normal level. In the present study, transverse sections through the caudalmost spinal segment of normal adult Sternarchus were examined. Proceeding rostrally from the caudal tip of the cord, the number of electromotor neurons increases monotonically to reach the normal number at a site 4-5 mm rostral to the caudal tip. Neither a massive overproduction of electromotor neurons nor a wave of neuronal death are observed during on-going growth of the normal spinal cord. The mechanisms by which the neuronal number is modulated are therefore different in the on-going normal growth of spinal cord versus regeneration of spinal cord in this species.     

The shortened spinal cord in tetraodontiform fishes

In teleosts, the spinal cord generally extends along the entire vertebral canal. The Tetraodontiformes, in which the spinal cord is greatly reduced in length with a distinct long filum terminale and cauda equina, have been regarded as an aberration. The aims of this study are: 1) to elucidate whether the spinal cord in all tetraodontiform fishes shorten with the filum terminale, and 2) to describe the gross anatomical and histological differences in the spinal cord among all families of the Tetraodontiformes. Representative species from all families of the Tetraodontiformes, and for comparison the carp as a common teleost, were investigated. In the Triacanthodidae, Triacanthidae, and Triodontidae, which are the more ancestral taxa of the Tetraodontiformes, the spinal cord extends through the entire vertebral canal. In the Triacanthidae and Triodontidae, the caudal half or more spinal segments of the spinal cord, however, lack gray matter and consist largely of nerve fibers. In the other tetraodontiform families, the spinal cord is shortened forming a filum terminale with the cauda equina, which is prolonged as far as the last vertebra. The shortened spinal cord is divided into three groups. In the Ostraciidae and Molidae, the spinal cord tapers abruptly at the cranium or first vertebra forming a cord‐like filum terminale. In the Monacanthidae, Tetraodontidae, and Diodontidae, it abruptly flattens at the rostral vertebrae forming a flat filum terminale. The spinal cord is relatively longer in the Monacanthidae than that in the other two families. It is suggested by histological features of the flat filum terminale that shortening of the spinal cord in this group progresses in order of the Monacanthidae, Tetraodontidae, and Diodontidae. In the Balistidae and Aracanidae, the cord is relatively long and then gradually decreased in dorso‐ventral thickness. J. Morphol. 276:290–300, 2015. © 2014 Wiley Periodicals, Inc.     

Origin of hydrogen required for fatty acid synthesis in isolated rat adipocytes.

Beef liver and beef spinal cord d-glycerate dehydrogenases have been shown to be extremely similar. No differences between the two enzymes could be shown by polyacrylamide electrophoresis, sodium dodecyl sulfate polyacrylamide electrophoresis, immunodiffusion, immunoelectrophoresis, or their response to certain inhibitors. Differences could be obtained, however, between the beef spinal cord enzyme and the hog spinal cord enzyme by immunodiffusion and immunoelectrophoresis.Only by the very sensitive technique of microcomplement fixation could a small but significant difference be shown between the beef liver and beef spinal cord enzymes. Like the beef liver and hog spinal cord enzymes, the beef spinal cord enzyme was not inhibited by high concentrations of serine or glycine. The enzyme was inhibited however by low concentrations of phosphohydroxypyruvate and by other phosphorylated compounds.     

Zebrafish Spinal Cord Repair Is Accompanied by Transient Tissue Stiffening

Severe injury to the mammalian spinal cord results in permanent loss of function due to the formation of a glial-fibrotic scar. Both the chemical composition and the mechanical properties of the scar tissue have been implicated to inhibit neuronal regrowth and functional recovery. By contrast, adult zebrafish are able to repair spinal cord tissue and restore motor function after complete spinal cord transection owing to a complex cellular response that includes axon regrowth and is accompanied by neurogenesis. The mechanical mechanisms contributing to successful spinal cord repair in adult zebrafish are, however, currently unknown. Here, we employ atomic force microscopy-enabled nanoindentation to determine the spatial distributions of apparent elastic moduli of living spinal cord tissue sections obtained from uninjured zebrafish and at distinct time points after complete spinal cord transection. In uninjured specimens, spinal gray matter regions were stiffer than white matter regions. During regeneration after transection, the spinal cord tissues displayed a significant increase of the respective apparent elastic moduli that transiently obliterated the mechanical difference between the two types of matter before returning to baseline values after the completion of repair. Tissue stiffness correlated variably with cell number density, oligodendrocyte interconnectivity, axonal orientation, and vascularization. This work constitutes the first quantitative mapping of the spatiotemporal changes of spinal cord tissue stiffness in regenerating adult zebrafish and provides the tissue mechanical basis for future studies into the role of mechanosensing in spinal cord repair.     

小鼠脊髓损伤模型的建立及其评价

通过对模型的制备模拟脊髓损伤,研究其病理和影像的变化及脊髓组织的病理分析,为后期的唔疗提供了实验信息。使用7～8周龄小鼠,咬除T9～T10棘突及相应椎板,用重物压迫脊髓,缝合皮肤,制成脊髓损伤模型。分不同的时间进行行为学评分及病理和影像学的检测。结果显示对照组在不同时间行为学评分较高,而实验组评分较低。脊髓损伤区出现明显的病理改变和影像学的改变。可见在实验组中小鼠脊髓损伤区无脊髓组织残留,且出现明显的组织和影像改变,在行为学上两组相比具有显著差异,适用于脊髓再生的研究,从而为进一步研究脊髓损伤提供了较为可靠的模型。