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1.
Significant regeneration of neural pathways following complete transection of the spinal cord has yet to be demonstrated. In the present study, we analyzed the ability of carbon filaments to function as a scaffold for the regrowth of injured axons in the rat spinal cord. Through the use of three different axonal tracing methods, severed spinal axons were observed growing on and between carbon filaments implanted into the completely transected rat spinal cord. Carbon filaments, by providing a favorable adhesive surface and also a possible guiding function, may prove useful in the treatment of spinal cord injury.  相似文献   

2.

Objective

In healthy subjects, spinal reflexes (SR) evoked by non-noxious tibial nerve stimulation consist of an early (60–120 ms latency) and an occasional late-appearing (120–450 ms latency) component in the ipsilateral tibialis anterior. In chronic (>1 year) complete spinal cord injured (cSCI) subjects early components are small or lacking while late components are dominant. Here we report on the modulation of SR by assisted locomotion in healthy and chronic motor cSCI subjects.

Methods

SR was evoked by tibial nerve stimulation at the terminal stance phase during assisted locomotion and was compared to SR recorded during upright stance.

Results

In chronic cSCI subjects only a late SR component was consistently present during upright stance. However during assisted locomotion, an early SR component appeared, while amplitude of the late SR component became small. In contrast, in healthy subjects the early SR component dominated in all conditions, but a small late component appeared during assisted locomotion.

Conclusion

A more balanced activity of early and late SR components occurred in both subject groups if an appropriate proprioceptive input was provided.

Significance

Early and late SR components are assumed to reflect the activity of separate neuronal circuits, which are associated with the locomotor circuitry possibly by shaping the pattern.  相似文献   

3.
OBJECTIVE: In spinal cord injured (SCI) subjects, exaggerated withdrawal reflexes associated with a dominant flexor pattern irrespective of stimulation site have been reported. In the present study, withdrawal reflex receptive field (RRF) was determined in complete SCI subjects (N=9). METHODS: Distributed electrical stimulation was applied to the sole of the foot, and reflexes in tibialis anterior, soleus, biceps femoris, and vastus lateralis muscles were recorded together with knee and ankle movement trajectories. A group of spinally intact subjects (N=10) were included as controls. With the subjects in supine position, stimulation was applied to 10 different sites on the foot sole. Based on the tibialis anterior reflex threshold for stimulation on the mid foot sole, two stimulus intensities (1.1 times the reflex threshold and 1.4 times the reflex threshold) were used for all 10 sites. RESULTS: In SCI subjects, dorsi-flexion dominated independent of stimulus site and the tibialis anterior RRF covered the entire foot sole in contrast to a well-defined tibialis anterior receptive field at the medial, distal foot sole in the spinally intact subjects. Further, the soleus RRF also covered the entire sole in the SCI subjects. The reflexes in biceps femoris and vastus lateralis muscles were small and associated with weak knee flexion at all 10 sites in the SCI subjects and in the controls. CONCLUSIONS: The RRF of the ankle flexor and the ankle extensor muscles both covered the entire sole of the foot indicating an expansion of the RRFs following spinal cord injury. The expansion is most likely due to lack of descending inhibitory control and/or increased sensitivity of the spinal reflex loop in the SCI subjects. SIGNIFICANCE: The study improves the understanding of spinal reflex control in spinal intact and spinal cord injured subjects.  相似文献   

4.
Sympathetic (SYMP) nerve activity in spinal intact neonatal swine is comprised of prominent bursts reflecting modulation by supraspinal structures involved in shaping central respiratory and baroreceptor activity. After spinal cord transection (SCT), we found no evidence of such modulation. SYMP activity was now related to the ventilatory cycle, exhibiting bursts only during lung inflation. Such activity suggests the emergence of latent spinal circuits which may have the capacity to regulate cardiovascular activity.  相似文献   

5.
Summary We have previously reported that cultured peripheral non-neuronal cells could be used as an adjunct to spinal cord reconstruction with the delayed nerve graft technique. The cultured cells appeared to enhance axonal regeneration and with their use the time it took for axons from the spinal cord stumps to reach the nerve graft was reduced. To gain insight into the possible mechanisms through which peripheral nonneuronal cells can foster CNS regeneration, we have now investigated the behaviour of the peripheral nonneuronal cells after implantation into the spinal cord. Autologous mixed non-neuronal cell cultures were prepared from cat sciatic nerve biopsies and labeled in culture with tritiated thymidine. The labeled cells were implanted so as to completely fill the gap in the spinal cord produced by a narrow slit transection. Light-and electron-microscopic autoradiography was used to identify the cells 3 and 7 days after implantation and to determine their proximity to, and possible interaction with, axons in the spinal cord stumps. The implanted peripheral cells were frequently found near spinal cord axons and axon terminals. Some of the labeled cells ensheathed axons in which case they displayed morphological characteristics of Schwann cells. Other labeled cells had characteristics of fibroblasts and were surrounded by an extracellular matrix rich in collagen fibrils. Many of the labeled cells contained phagocytosed myelin debris. These observations are consistent with the implanted cells acting to enhance regeneration in the spinal cord either by direct interaction with axons (ensheathment) or indirectly via the production of soluble neuronotrophic factors or a favorable extracellular matrix. The ability of the implanted cells to rapidly move into the spinal cord stumps and attain positions close to spinal cord axons would be an important factor for any of these mechanisms.Supported by grants from the Veterans Administration and the National Institutes of Health (NS-14413)  相似文献   

6.
目的探讨生物素葡聚糖胺(BDA)神经示踪技术及脊髓半横断损伤模型在大鼠脊髓损伤修复的实验研究中应用。方法采用成年Sprague-Dawley大鼠,分为脊髓致伤组(n=10)和致伤对照组(n=10)。致伤组动物在相当于T7椎板水平横行剪断脊髓的后2/3;对照组动物术中仅切除椎板,不切断脊髓。术后第15d,右侧开颅,用10?A示踪剂注入右侧的感觉运动区皮质内。2周后取出大脑和脊髓组织,采用自由漂乳法行BDA染色显影。术后实验动物功能测评采用BBB运动功能评分,所得数据采用Student'st-test进行统计学原理。结果(1)脊髓损伤组动物双后肢瘫痪,BBB运动功能评分明显低于损伤对照组,统计学比较差异十分显著(P<0.01);(2)BDA顺行示踪显示大脑皮层BDA注射区内见大脑皮层的锥体细胞及其发出的轴突呈阳性染色,BDA阳性染色的皮质脊髓束神经纤维在同侧中脑、桥脑及延髓的腹侧面行走,在锥体交叉后皮质脊髓束主要在对侧脊髓白质的后索中行走。在致伤组动物中,位于脊髓白质后索中的皮质脊髓束纤维在脊髓损伤处终止;对照组皮质脊髓束BDA染色可一直延伸至L1水平。结论大鼠半脊髓切断结合应用BDA顺行示踪技术可以对脊髓损伤后的神经修复状况进行可靠的形态学评判,是研究脊髓损伤后中枢神经纤维再生修复较为理想的动物模型  相似文献   

7.
Mechanical spinal cord injury (SCI) initiates a cascade of pathochemical and pathophysiological events, collectively known as the secondary injury. There has been a long-standing interest in understanding the activation and involvement of proteases in this secondary injury process. Several proteases including the calpains, caspases and matrix metalloproteinases are activated by perturbations to the spinal cord and have been linked to cell death following SCI and in other models of CNS disease and insult. Cathepsin B (Cath B), a potent lysosomal protease, has also been implicated in the pathology of CNS diseases including brain tumors, Alzheimer's disease, amyotrophic lateral sclerosis and stroke. Previously, we reported significant increases in Cath B mRNA and protein expression following contusion-SCI. This characterization of Cath B continues with the experiments reported herein, which were designed to examine Cath B enzymatic activity and cellular localization following contusion-SCI in the rat. Cath B enzymatic activity was significantly increased in the injury epicenter at 5 and 7 days post-injury and was highly correlated with increases in the active forms of the Cath B protein reported earlier. Furthermore, the immunohistochemical analyses revealed that the post-injury increases in expression and enzymatic activity at the injury epicenter were due to the presence of a large and diverse population of inflammatory cells. However, in areas adjacent to the injury epicenter, it appears that parenchymal neurons may also contribute to these increases. Our findings coupled with the documented role of Cath B in other CNS pathologies make this potent protease an attractive candidate for involvement in the tissue destruction associated with the secondary injury cascade following SCI.  相似文献   

8.
目的研究促甲状腺释放激素(TRH)类似物,YM-14673大鼠脊髓损伤后水肿的影响。方法用改良Allen氏法建立大鼠脊髓损伤模型,分设正常组、对照组和治疗组,治疗组在损伤后15分钟注射YM-14673,用称重法测量脊髓的水含量,公式:(湿重-干重)÷湿重×100%。结果对照组示伤后24小时脊髓水肿,治疗组显示在24小时脊髓水肿减轻。结论早期应用TRH类似物,YM-14673可减轻脊髓损伤后的脊随水肿。  相似文献   

9.
胚胎脊髓移植在恢复损伤脊髓传导功能中的作用   总被引:3,自引:1,他引:2  
目的:探讨胚胎脊髓移植在恢复损伤脊髓传导功能中的作用。方法:将E14胚胎脊髓植入成鼠损伤脊髓后30、45、60天时,用单位放电记录技术观察了正常脊髓神经元和移植物神经元的自发放电活动,及其对刺激坐骨神经、红核和同时刺激的反应。结果:正常脊髓神经元的自发单位放电多是一个低频的单发脉冲活动。无论选择那种刺激方式,都可见兴奋、抑制和无反应三种反应。术后30天时,胚胎神经元的自发单位放电以高频电脉冲活动为主,簇状放电所占比例较大,对刺激有反应的放电单位数也较少;随着动物存活时间的延长,这些单位放电的情况逐渐向着低频、单脉冲以及高反应率的方向发展。至术后60天时,胚胎神经元单位放电的频率、形式以及对刺激的反应情况都变得和正常神经元的相似。结论:胚胎神经元移植后经历了一个逐渐发育分化过程,在这个过程中它们有可能逐渐和宿主神经元形成了功能性突触连接。  相似文献   

10.
A subdural inflatable microballoon was used to induce closed traumatic contusion to adult rat spinal cord. This spinal cord injury model was associated with reproducible and graded neurological deficits and histopathological alterations. At various delays after injury, transplantations of syngeneic adult cultured dorsal root ganglion-derived Schwann cells were performed into the spinal cord lesion. The transplants were well integrated and reduced the microcystic posttraumatic cavitation as well as the gliosis. Schwann cells transplants were invaded by numerous regenerating neurites most of which, based upon their neurotransmitter contents, seem to originate from the dorsal root ganglion.  相似文献   

11.
Abstract

Effects ofa single, huge dose of methylprednisolone on post-traumatic spinal cord blood flow (SCBF), evoked potentials and histological changes were studied in a rat model ofspinal cord injury. The purpose of this study was to assess the optimal dose of methylprednisolone for the treatment of rat spinal cord injury. Twenty-five male Wistar rats were subjected to an acute clip compression injury at 51 g for 1 min at CB-T1, and then received an intravenous bolus injection of one of the following 30 min after injury: vehicle, 30, 60, 120 or 240 mg kg -1 methylprednisolone. SCBF was measured at the injury site and an adjacent area with the' hydrogen clearance technique. Sensory evoked potentials following sciatic stimulation were recorded from the somatosensory and cerebellar cortices. Descending volleys were recorded from T9-10 spinal cord following cerebellar stimulation. SCBF and evoked potential recordings were repeated until perfusion-fixation at 4 h after injury. After injury, SCBF at both levels significantly dropped, and all evoked potentials disappeared in all animals. None of the doses of methylprednisolone improved post-traumatic SCBF, or evoked potentials. Qua;ntitative histological assessment ,of the injured cords revealed no significant differences in hemorrhages or cavitation in the spinal cord among the treatment groups. This study showed that a single huge dose of methylprednisolone from 30 to 240 mg kg- 1 had no beneficial effects on the traumatized rat spinal cord in the acute stage. [Neural Res 1997; 19: 289–299]  相似文献   

12.
The adult mammalian CNS undergoes plastic changes in response to injury. To investigate such changes in spinal cord, functional magnetic resonance imaging (fMRI) was applied in rats subjected to complete transection of the mid-thoracic spinal cord. Blood oxygenation level-dependent (BOLD) contrasts were recorded in the distal spinal cord different times after injury (3, 7, and 14 days, and 1, 3, and 6 months) in response to electrical hind limb stimulation. Functional MRI demonstrated a substantial increase of neuronal activation in the ipsilateral dorsal horn after injury. Notably, 0.5 mA, which did not evoke activation in the normal spinal cord and was considered a non-painful stimulus, induced significant BOLD responses in the dorsal horn after injury. Increased sensitivity was also seen in response to 1.0 mA stimulation. Our results suggest exaggerated responsiveness of spinal neurons after spinal cord injury. Reorganization in the injured spinal cord has been shown to involve the amplification of peripheral inputs and implicated as one underlying mechanism causing neuropathic pain and autonomic dysreflexia. Since BOLD signals can demonstrate such plastic changes in spinal cord parenchyma, we propose fMRI as a method to monitor functional reorganization in the spinal cord after injury. Combining brain and spinal cord fMRI allows the visualization of neuronal activities along the entire neuroaxis and thereby an evaluation of the different plastic responses to CNS injuries that occur in the brain and the spinal cord.  相似文献   

13.
Reorganization of neural circuits within the central nervous system following injury appears to be a means of compensatory mechanism for loss of function. Reorganization following spinal cord injury is known to evoke changes at the cortical and spinal cord levels. Recent studies, however, provide evidence of enhanced brainstem reflexes and alterations in excitatory and inhibitory interneuronal brainstem circuits, suggesting that reorganization following spinal cord injury occurs also at the brainstem level. Reversal of these changes by continuous intrathecal baclofen infusion to normal levels or beyond indicates strong GABAergic involvement. Rapid changes in the blink reflex and its prepulse inhibition following intrathecal baclofen bolus application that parallel clinical changes in muscle hypertonia suggest a muscle tone regulating effect of baclofen at the brainstem level. Enhanced brainstem reflexes in spinal cord injury patients may be the consequence of decreased GABA-mediated inhibition and/or strengthening of facilitatory connections due to either direct or indirect plastic changes occurring at the brainstem level. Modulation of brainstem reflexes by baclofen may foster the understanding of pathophysiological mechanisms underlying diseases with increased brainstem activity. Rehabilitation after central nervous system injury will always be a challenge, but understanding the mechanisms of reorganization of undamaged neural pathways may help to develop better strategies for enhancing neuronal plasticity and for implementing neuronal reorganization into carefully planned therapy.  相似文献   

14.
组织工程脊髓移植治疗大鼠脊髓半切块状损伤   总被引:1,自引:0,他引:1  
目的 研究组织工程脊髓移植治疗大鼠脊髓半切块状损伤的疗效.方法 以聚乳酸-羟基乙酸(PLGA)为细胞支架,多聚赖氨酸为细胞外基质,神经十细胞(NSCs)为种子细胞,体外构建组织工程脊髓.制作大鼠T10脊髓右半切块状损伤模型,随机分成3组:实验组在损伤区移植组织工程脊髓,对照组A移植NSCs,对照组B移植PLGA.移植治疗12周,每周均行BBB评分定量评价肢体运动功能.伤后第12周辣根过氧化物酶(HRP)神经逆行示踪评价脊髓传导束的恢复程度,并取损伤处脊髓组织行免疫组织化学染色,观察移植区的形态结构修复.结果 伤后12周实验组的BBB运动功能评分较对照组明显提高,差异有统计学意义(P<0.05).HRP神经逆行示踪显示:实验组鼠右侧大脑组织中可见大量的HRP标记阳性神经元,而两对照组仅见有少量HRP阳性神经元;免疫组织化学染色显示:实验组移植区NF阳性神经元和GAP-43阳性神经轴索数量较多,修复了缺损,而对照组极少,仍留下不同程度的缺损.结论 组织工程脊髓移植治疗促进了半切块状损伤脊髓的形态结构修复和功能恢复,疗效明显优于单纯的NSCs移植和PLGA移植.  相似文献   

15.
Secondary injury following traumatic spinal cord injury is induced by the activation of a number of cellular and molecular changes. RhoA, a small GTPase, regulates the organization of the actin cytoskeleton, gene expression, cell proliferation, and has been implicated in the regenerative process. This study was undertaken to investigate the involvement of the RhoA signaling pathway in the secondary injury that follows traumatic spinal cord injury in rats. RhoA mRNA and protein expressions were enhanced significantly in the injured spinal cord 1 week after surgery (P<0.05, ANOVA). C3 exozyme (RhoA inhibitor), Y-27632 (selective Rho kinase inhibitor), and Fasudil (non-selective protein kinase inhibitor) were administered after spinal cord injury, and the subjects were evaluated for 5 weeks as per BBB locomotor score. Poor rat response interrupted the C3 experiment. Y-27632 slightly, but significantly (P<0.05, ANOVA), delayed the recovery. Fasudil significantly improved the BBB score (P<0.05, ANOVA). In conclusion, spinal cord injury activates the RhoA/Rho-kinase alpha, beta associated pathway. However, their role in secondary injury or in the improvement of functional recovery remains unclear. Fasudil might exert a cytoprotective effect by mechanisms other than inhibiting Rho-kinase alpha, beta.  相似文献   

16.
Objectives  Spinal cord injury results in loss of supraspinal control of sympathetic outflow, yet preservation of spinal reflexes. Given the importance of reflex activation of sympathetic vasoconstrictor neurones to the generation of autonomic dysreflexia, we assessed the input–output relationship of the spinal somatosympathetic reflex induced by electrical activation of cutaneous afferents over the lower abdominal wall. Methods  In 13 spinal cord-injured subjects (C4-T10) we tested the hypothesis that the magnitude and duration of the vasoconstriction is directly related to the magnitude and duration of the stimulus train. Cutaneous vasoconstriction was measured with photoelectric plethysmography over a finger and toe; continuous blood pressure was recorded by radial artery tonometry, heart rate by ECG chest electrodes and sweat release by skin conductance. Four sets of trains of cutaneous electrical stimuli (20 Hz 1 s, 20 Hz 20 s, 20 Hz 1 s alternating on-and-off for 20 s and 1 Hz 20 s) were applied to the abdominal wall (10 mA) at 2-min intervals. Results  Nine subjects showed vasoconstrictor responses to the stimulus trains. On average, both the magnitude and duration of the responses were similar irrespective of the type of stimulus train. Interpretation  We conclude that there is a non-linear relationship between somatic inputs and sympathetic vasoconstrictor outputs, and argue that a sustained vasoconstriction need not imply continuous sensory input to the spinal cord.  相似文献   

17.
The goal of this study was to determine the effect of chronic mid-thoracic spinal cord transection on the time course of external urethral sphincter (EUS) and bladder activity associated with micturition events in the rat. Adult female Sprague–Dawley rats, either spinally intact or transected (T9–T10), were anesthetized with urethane and set up for continuous flow urodynamic recording of bladder intravesical pressure (BP) and EUS electromyography (EMG). Spinal transections were performed under isoflurane anesthesia 1–8 weeks prior to the terminal experiment. Four major differences between intact and transected rats were observed: 1) While the frequency of micturition events in the intact rat was dependent upon the rate of bladder filling, the bladder contraction and associated EUS activation in transected rats exhibited an intrinsic rhythm that was independent of the rate of bladder filling and post-transection survival time. 2) EUS activation was augmented at the beginning of active bladder contraction in the transected rat, indicating an amplified guarding reflex. 3) Phasic EUS activity at the peak of bladder contraction (EUS bursting) in the intact rat was markedly reduced or absent in the transected rat. 4) The sustained tonic EUS activity following bladder relaxation in the intact rat was absent in the transected rat. These data are discussed in the context of understanding the pathophysiology of spinal cord injury (SCI) induced destrusor-sphincter dyssynergia (DSD).  相似文献   

18.
This study was initiated due to an NIH “Facilities of Research — Spinal Cord Injury” contract to support independent replication of published studies that appear promising for eventual clinical testing. We repeated a study reporting the beneficial effects of recombinant human erythropoietin (rhEPO) treatment after spinal cord injury (SCI). Moderate thoracic SCI was produced by two methods: 1) compression due to placement of a modified aneurysm clip (20 g, 10 s) at the T3 spinal segment (n=45) [followed by administration of rhEPO 1000 IU/kg/IP in 1 or 3 doses (treatment groups)] and 2) contusion by means of the MASCIS impactor (n = 42) at spinal T9 (height 12.5 cm, weight 10 g) [followed by the administration of rhEPO 5000 IU/kg/IP for 7d or single dose (treatment groups)]. The use of rhEPO following moderate compressive or contusive injury of the thoracic spinal cord did not improve the locomotor behavior (BBB rating scale). Also, secondary changes (i.e. necrotic changes followed by cavitation) were not significantly improved with rhEPO therapy. With these results, although we cannot conclude that there will be no beneficial effect in different SCI models, we caution researchers that the use of rhEPO requires further investigation before implementing clinical trials.  相似文献   

19.
目的观察缺氧诱导因子-1α(HIF-1α)在大鼠脊髓缺血再灌注损伤(SCII)中的表达变化及其意义。方法制备大鼠脊髓缺血再灌注损伤模型,分别于再灌注后8h、12h、24h,3d和5d取腰骶段的脊髓,以假手术组大鼠相同阶段的脊髓为对照,采用Westernblot法和免疫组织化学检测伤后脊髓组织中HIF-1α的表达变化。结果再灌注8h左右HIF-1α在整个脊髓灰质开始表达上调,在24h达峰值,在伤后3d表达回落,5d显著减少,灰度值在8h、12h、24h,3d和5d不同时相,分别为(211.39±5.58)μm2,(184.53±6.56)μm2,(167.39±5.76)μm2,(198.44±3.98)μm2和(228.39±2.87)μm2,分别与假手术组比较差异有显著性意义(P〈0.05)。HIF-1a在灰质中的表达以中央管周围和前角、后角最为显著。再灌注24h和3dHIF-1a在脊髓白质出现弱的表达,灰度值分别为(238.154-6.87)μm2和(236.87±7.41)μm2,分别与假手术组比较差异有显著性意义(P〈0.05)。但在白质后索,HIF-1a的表达相对较强。HIF-1α在灰质中主要定位于神经元和星形胶质细胞,在白质中主要定位于神经胶质细胞。结论脊髓缺血再灌注损伤后,HIF-1α呈现时序性的表达变化,这可能是脊髓缺血再灌注损伤的重要适应性调节机制之一。  相似文献   

20.
BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy. OBJECTIVE: To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN: Completely randomized controlled study. SETTING: Department of Neurosurgery, Xiangya Hospital of Central South University. MATERIALS: Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS: This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping: 55 rats were randomly divided into model group (n = 40) and sham surgery group (n = 15). In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES: Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. Paraplegia was evaluated as 0 point, and complete normality as  相似文献   

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