Low Thoracic Spinal Cord Injury Research Articles

Orthotic walking outcome of persons with motor complete low thoracic spinal cord injury-a retrospective study.

Retrospective study. To analyse the orthotic walking outcome of patients with Low Thoracic Spinal Cord Injury (LT-SCI). The Rehabilitation Institute at Christian Medical College, Vellore, India. Data between January 2005 and June 2015 were retrospectively collected from electronic medical reports of patients with motor complete LT- SCI who were admitted for the comprehensive rehabilitation program. The orthotic walking outcome of these patients was measured by the Walking index for SCI version II (WISCI II). Demographical and clinical parameters were measured and their association with the walking outcome was analyzed using regression analysis. A total of 430 patients were identified within the study period. Eighty-five percent of people (n = 365) achieved walking at the time of discharge (WISCI II level 12 = 260 and level 9 = 105). Out of 11 demographical and clinical parameters considered, eight of them were found to be significant predictors of walking in the univariate analysis. Age less than 30 years had the highest odds of predicting WISCI II level 9 and level 12 than those older in the multivariate analysis (OR 17.58; 95% CI 7.35-42.03). Single neurological level T12 increased the chance of achieving WISCI II level 12 by 10 times (OR 10.2; 95% CI 3.8-27.36). Orthotic walking for persons with motor complete low thoracic spinal cord injury is an achievable goal through a comprehensive rehabilitation program. The factors identified in this study will help rehabilitation professionals strategically select the ideal candidate for orthotic gait training.

Partial Restoration of Spinal Cord Neural Continuity via Sural Nerve Transplantation Using a Technique of Spinal Cord Fusion.

BackgroundSpinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. Based on our previous experimental results of spinal cord fusion (SCF) in mice, rats, beagles, and monkeys, we developed a surgical protocol of SCF for paraplegic human patients. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction.MethodsWe conducted a clinical trial (ChiCTR2000030788) and performed SNT in 12 fully paraplegic patients due to SCI between T1 and T12. We assessed pre- and postoperative central nerve pain, motor function, sensory function, and autonomic nerve function. Conduction of action potentials across the sural nerve transplant was evaluated. Neural continuity was also examined by diffusion tensor imaging (DTI).ResultsAmong the 12 paraplegic patients enrolled in this clinical trial, seven patients demonstrated improved autonomic nerve functions. Seven patients had clinically significant relief of their symptoms of cord central pain. One patient, however, developed postoperative cord central pain (VAS: 4). Five patients had varying degrees of recovered sensory and/or motor functions below the single neurologic level 1 month after surgery. One patient showed recovery of electrophysiologic, motor-evoked potentials 6 months after the operation. At 6 months after surgery, DTI indicated fusion and nerve connections of white cord and sural nerves in seven patients.ConclusionSNT was able to fuse the axonal stumps of white cord and sural nerve and at least partially improve the cord central pain in most patients. Although SNT did not restore the spinal cord continuity in white matter in some patients, SNT could restore spinal cord continuity in the cortico-trunco-reticulo-propriospinal pathway, thereby restoring in part some motor and sensory functions. SNT may therefore be a safe, feasible, and effective method to treat paraplegic patients with SCI. Future clinical trials should be performed to optimize the type/technique of nerve transplantation, reduce surgical damage, and minimize postoperative scar formation and adhesion, to avoid postoperative cord central pain.Clinical Trial Registration[http://www.chictr.org.cn/showproj.aspx?proj=50526], identifier [ChiCTR2000030788].

Hemorrhage and Locomotor Deficits Induced by Pain Input after Spinal Cord Injury Are Partially Mediated by Changes in Hemodynamics.

Nociceptive input diminishes recovery and increases lesion area after a spinal cord injury (SCI). Recent work has linked these effects to the expansion of hemorrhage at the site of injury. The current article examines whether these adverse effects are linked to a pain-induced rise in blood pressure (BP) and/or flow. Male rats with a low-thoracic SCI were treated with noxious input (electrical stimulation [shock] or capsaicin) soon after injury. Locomotor recovery and BP were assessed throughout. Tissues were collected 3 h, 24 h, or 21 days later. Both electrical stimulation and capsaicin undermined locomotor function and increased the area of hemorrhage. Changes in BP/flow varied depending on type of noxious input, with only shock producing changes in BP. Providing behavioral control over the termination of noxious stimulation attenuated the rise in BP and hemorrhage. Pretreatment with the α-1 adrenergic receptor inverse agonist, prazosin, reduced the stimulation-induced rise in BP and hemorrhage. Prazosin also attenuated the adverse effect that noxious stimulation has on long-term recovery. Administration of the adrenergic agonist, norepinephrine 1 day after injury induced an increase in BP and disrupted locomotor function, but had little effect on hemorrhage. Further, inducing a rise in BP/flow using norepinephrine undermined long-term recovery and increased tissue loss. Mediational analyses suggest that the pain-induced rise in blood flow may foster hemorrhage after SCI. Increased BP appears to act through an independent process to adversely affect locomotor performance, tissue sparing, and long-term recovery.

Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

—Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

A porcine model for studying the cardiovascular consequences of high-thoracic spinal cord injury.

We have developed a novel porcine model of high-thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level. We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post-SCI. We demonstrate that the high-thoracic SCI model, but not a low-thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II. We additionally conducted a proof-of-concept long-term (12weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long-term drug studies prior to translation to the clinic. Cardiovascular disease is a leading cause of morbidity and mortality in the spinal cord injury (SCI) population, especially in those with high-thoracic or cervical SCI. With this in mind, we aimed to develop a large animal (porcine) model of high-thoracic (T2 level) contusion SCI and compare the haemodynamic and neurohormonal responses of this injury against a low-thoracic (T10 level) model. Ten Yorkshire pigs were randomly subjected to 20cm weight drop contusion SCI at either the T2 or the T10 spinal level. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored until 4h post-SCI. Plasma noradrenaline (NA), aldosterone and angiotensin II (ANGII) were measured pre-SCI and at 30, 60, 120 and 240min post-SCI. Additionally, two Yucatan pigs were subjected to T2-SCI and survived up to 12weeks post-injury to demonstrate the efficacy of this model for long-term survival studies. Immediately after T2-SCI, SBP, MAP and HR increased (P<0.0001). Between decompression (5min post-SCI) and 30min post-decompression in T2-SCI, SBP and MAP were lower than pre-SCI (P<0.038). At 3 and 4h after T2-SCI, SBP remained lower than pre-SCI (P=0.048). After T10-SCI, haemodynamic indices remained largely unaffected. Plasma NA was lower in T2- vs. T10-SCI post-SCI, whilst aldosterone and ANGII were higher. Both chronically injured pigs demonstrated a vast reduction in SBP at 12weeks post-SCI. Our model of T2-SCI causes a rapid and sustained alteration in neurohormonal control and cardiovascular function, which does not occur in the T10 model.

Systemic microcirculation dysfunction after low thoracic spinal cord injury in mice

BackgroundSpinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction or failure of multiple organs. The systemic microcirculation disturbance that contributes to the complications associated with SCI remains to be clarified. MethodsWe used male mice (29–32 g) and modified weight-drop injury at T10 to evaluate the systemic microcirculation dysfunction during the first 2 weeks after SCI. We determined permeability and microvascular blood flow in several organs and evaluated their vasomotor function. We also measured circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), circulating pericyte progenitor cells (CPPCs), and serum proinflammatory cytokines. ResultsThe endothelial permeability of almost all organs increased after SCI. Microvascular blood flow decreased in the bladder and kidney and increased in the spleen and was accompanied by endothelial vasomotor dysfunction. SCI also induced an increase in CECs, CEPCs, and CPPCs in peripheral blood. Finally, we confirmed changes in a systemic cytokine profile (interleukin [IL]-3, IL-6, IL-10, IL-13, granulocyte colony-stimulating factor, and regulated on activation normal T cell expressed and secreted) after SCI. ConclusionsThese data indicate that a systemic microcirculation disturbance occurs after SCI. This information may play a key role in the development of effective therapeutic strategies for SCI.

Time-dependent changes in paw carrageenan-induced inflammation above and below the level of low thoracic spinal cord injury in rats.

This was an animal study. Local inflammation is attenuated below high thoracic SCI, where innervation of major lymphoid organs is involved. However, whether inflammatory responses are affected after low thoracic SCI, remains undetermined. The aim of this study was to characterize the influence of low thoracic SCI on carrageenan-induced paw swelling in intact and paralyzed limbs, at acute and subacute stages. University and hospital-based research center, Mexico City, Mexico. Rats received a severe contusive SCI at T9 spinal level or sham injury. Then, 1 and 15 days after lesion, carrageenan or vehicle was subcutaneously injected in forelimb and hindlimb paws. Paw swelling was measured over a 6-h period using a plethysmometer. Swelling increased progressively reaching the maximum 6 h post-carrageenan injection. Swelling increase in sham-injured rats was approximately 130% and 70% compared with baseline values of forelimbs and hindlimbs, respectively. Paws injected with saline exhibited no measurable swelling. Carrageenan-induced paw swelling 1-day post-SCI was suppressed in both intact and paralyzed limbs. Fifteen days post-injury, the swelling response to carrageenan was completely reestablished in forelimbs, whereas in hindlimbs it remained significantly attenuated compared with sham-injured rats. SCI at low spinal level affects the induced swelling response in a different way depending on both, the neurological status of challenged regions and the stage of injury. These findings suggest that neurological compromise of the main immunological organs is not a prerequisite for the local swelling response to be affected after injury.

The effect of myelotomy following low thoracic spinal cord compression injury in rats

Myelotomy is a surgical procedure allowing removal of extravasated blood and necrotic tissue that is thought to attenuate secondary injury as well as promote recovery in experimental spinal cord injury (SCI) models and humans. Here we examined in rat whether myelotomy at 48 h after low-thoracic compressive SCI provided any benefit over a 12 week period. Compared to animals receiving SCI alone, myelotomy worsened BBB scores (p < 0.05) and also did not improve plantar stepping, ladder climbing, urinary bladder voiding or sensory function (thermal latency) during the 12-week period. Quantitative analyses of tissue sections at 12 weeks showed that myelotomy also did not reduce lesion volume nor alter immunohistochemical markers of axons in spared white matter bridges, microglia, astrocytes or serotinergic fibres. However, myelotomy reduced synaptophysin expression, a marker of synaptic plasticity. We conclude that further studies are required to evaluate myelotomy after SCI. (142 words).

The effect of level of injury and physical activity on heart rate variability following spinal cord injury

Objective/Background: To assess frequency domain heart rate variability (HRV) parameters at rest and in response to postural autonomic provocations in individuals with spinal cord injury (SCI) and investigate the autonomic influences on the heart of different physical activities.Design: Cross-sectional study.Methods: Ten subjects with complete cervical SCI and fourteen subjects with complete low thoracic SCI were prospectively recruited from the community and further divided in sedentary and physically active groups, the latter defined as regular weekly 4 hour physical activity for the preceding 3 months. Sixteen healthy individuals matched for sex and age were recruited to participate in the control group. The Low Frequency (LF), High Frequency (HF) powers and the LF/HF ratio of HRV were measured from continuous electrocardiogram (ECG) recordings at rest and after sitting using a fast Fourier transformation.Outcome measures: The LF,HF, and the LF/HF ratio at rest and after sitting.Results: A significant decrease in all HRV parameters in patients with SCI was found compared to controls. The change in HF, LF and LF/HF following sitting maneuver was significantly greater in controls as compared with the SCI group and greater in subjects with paraplegia as compared to subjects with tetraplegia. Better HRV values and enhanced vagal activity appears to be related to the type of physical activity in active subjects with paraplegia.Conclusion: In this cohort of subjects spectral parameters of HRV were associated with the level of the injury. Passive standing was associated with higher HRV values in subjects with paraplegia.

Postural regulatory strategies during quiet sitting are affected in individuals with thoracic spinal cord injury

Thoracic spinal cord injury (SCI) can have significant negative consequences, which can affect the ability to maintain unsupported sitting. The objectives of this study were to compare postural control of individuals with high- and low-thoracic SCI to able-bodied people and evaluate the effects of upper-limb support on postural control during quiet sitting. Twenty-five individuals were recruited into: (a) high-thoracic SCI; (b) low-thoracic SCI; and (c) able-body subgroups. Participants were seated and asked to maintain a steady balance in the following postures: (1) both hands resting on thighs; (2) both arms crossed over the chest; and (3) both arms extended. Center of pressure (COP) fluctuations were evaluated to compare postural performance between groups and different postures. Results showed that individuals with high- and low-thoracic SCI swayed more compared to the able-bodied group regardless of upper-limb support. No differences between the two SCI groups were observed, but the neurological level of injury was correlated to postural performance implying that those with higher injuries swayed more and faster. Unsupported sitting was more unstable in comparison to supported sitting posture, especially in the anterior-posterior direction. The velocity of postural sway was not different between groups, but the results suggest that postural regulation had unique effect during different postures in different groups. These results imply reduced postural stability after thoracic SCI. Overall, the way individuals with high-thoracic SCI achieved stability was different from that of individuals with low-thoracic SCI, suggesting different postural regulation strategies.

Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury

Spinal cord injury (SCI) can result in paralysis of trunk muscles, which can affect sitting balance. The objective of this study was to analyze trunk muscle coordination of individuals with thoracic SCI and compare it to able-body individuals. A total of 27 individuals were recruited and subdivided into: (a) high thoracic SCI; (b) low thoracic SCI; and (c) able-body groups. Participants were seated and asked to lean their trunk in eight directions while trunk muscle activity was recorded. Muscle coordination was assessed using the non-negative matrix factorization (NMF) method to extract muscle modules, which are the synergistic trunk muscle activations, and their directional activation patterns. Our results showed that individuals with SCI used less muscle modules, more co-contractions, and less directional tuning, compared to able-bodied people. These results suggest impaired and simplified muscle coordination due to the loss of supraspinal input after SCI. Observed variability in muscle coordination within SCI groups also suggests that other mechanisms such as spasticity and muscle stretch reflexes or individual factors such as experience and training contributed to the postural muscle synergies. Overall, muscle coordination deficits revealed impaired neuromuscular strategies which provide implications for rehabilitation of trunk muscles during sitting balance after SCI.

Paraplegia and transtibial amputation: successful ambulation after dual disability: a retrospective case report.

This is a single-subject case report. The objective is to describe the unique rehabilitation outcome of an individual with motor complete T12 paraplegia and a right transtibial amputation. This study was conducted at the Department of Physical Medicine and Rehabilitation of Christian Medical College in India. A 42-year-old policeman presented to our rehabilitation centre with motor complete T12 paraplegia and right transtibial amputation, 3 months following a road traffic accident. As the patient's goal was to walk, he was given a trial of independent ambulation with a customized prosthesis on the right side and a regular knee ankle foot orthosis (KAFO) on the left side. At the end of 12 weeks of rehabilitation, the patient was able to walk independently with the prosthesis/orthosis and bilateral elbow crutches. His Walking Index for Spinal Cord Injury (WISCI) score improved from 0/20 to 12/20 points. The scope of functional ambulation should not get restricted for a person with low thoracic spinal cord injury even when there is concurrent transtibial amputation.

Pelvic floor electrophysiology in spinal cord injury.

The study aimed to investigate sacral peripheral nerve function and continuity of pudendal nerve in patients with chronic spinal cord injury (SCI) using pelvic floor electrophysiological tests. Twelve patients with low cervical or thoracic SCI were prospectively included. Quantitative external anal sphincter (EAS) muscle electromyography (EMG), pudendal nerve terminal motor latency (PNTML) testing, bulbocavernosus reflex (BCR) testing and pudendal short-latency somatosensory-evoked potential (SEP) measurement were performed. In EAS muscle EMG, two patients had abnormal increased spontaneous activity and seven prolonged motor unit potential duration. PNTML was normal in 10 patients. BCR was present with normal latency in 11 patients and with prolonged latency in one. The second component of BCR could be recorded in four patients. SEPs showed absent cortical responses in 11 patients and normal latency in one. Pudendal nerve and sacral lower motor neuron involvement are significantly associated with chronic SCI, most prominently in EAS muscle EMG. The frequent finding of normal PNTML latencies supports earlier concerns on the utility of this test; however, BCR and pudendal SEPs may have clinical relevance. As intact peripheral nerves including pudendal nerve are essential for efficient supportive therapies, pelvic floor electrophysiological testing prior to these interventions is highly recommended.

Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia.

People with spinal cord injury (SCI) have an altered afferent input to the thermoregulatory center, resulting in a reduced efferent response (vasomotor control and sweating capacity) below the level of the lesion. Consequently, core body temperature rises more rapidly during exercise in individuals with SCI compared with people who are able-bodied. Cooling strategies may reduce the thermophysiological strain in SCI. The aim of this study was to examine the effects of a cooling vest on the core body temperature response of people with a thoracic SCI during submaximal exercise. Ten men (mean age=44 years, SD=11) with a thoracic lesion (T4-T5 or below) participated in this randomized crossover study. Participants performed two 45-minute exercise bouts at 50% maximal workload (ambient temperature 25°C), with participants randomized to a group wearing a cooling vest or a group wearing no vest (separate days). Core body temperature and skin temperature were continuously measured, and thermal sensation was assessed every 3 minutes. Exercise resulted in an increased core body temperature, skin temperature, and thermal sensation, whereas cooling did not affect core body temperature. The cooling vest effectively decreased skin temperature, increased the core-to-trunk skin temperature gradient, and tended to lower thermal sensation compared with the control condition. The lack of differences in core body temperature among conditions may be a result of the relative moderate ambient temperature in which the exercise was performed. Despite effectively lowering skin temperature and increasing the core-to-trunk skin temperature gradient, there was no impact of the cooling vest on the exercise-induced increase in core body temperature in men with low thoracic SCI.

Peripheral nervous system involvement in chronic spinal cord injury.

Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Twelve subjects with chronic low cervical or thoracic SCI were included prospectively. Needle electromyography was done in 10 different muscles in each subject bilaterally. Nerve conduction studies (NCS) were conducted in the fibular, tibial, and femoral motor and fibular and sural sensory nerves. Half the subjects had widespread abnormal spontaneous activity (SA), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. The presence of widespread electrophysiologic changes outside entrapment sites indicates that SCI has a significant impact on the entire PNS, affecting the motor part predominantly.

Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI.

Diagnosis and Management of Stress Urinary Incontinence in Females With Neurogenic Disease

Women with a wide variety of neurological conditions, including multiple sclerosis (MS), Parkinson’s disease (PD), cerebrovascular accidents (CVA), and spinal cord injury (SCI) frequently develop neurovesical dysfunction, commonly resulting in what is often called neurogenic bladder (NGB). The most common manifestations of NGB are urinary urgency, frequency, and urgency urinary incontinence (UUI). However, because many women with NGB conditions lead active lifestyles and are at an age when stress urinary incontinence (SUI) is prevalent, indeed, SUI is not uncommon in affected women. It is also true that, in some conditions, SUI may be a direct result of the neurological insult, for example, patients with low thoracic or lumbar SCI. Thus, deciphering the cause of urinary incontinence in patients with NGB is often complex, yet vital to developing optimal management strategies. This review focuses on the recent literature regarding both the diagnosis and treatment of SUI in women with NGB. In particular, specific strategies that may be essential in evaluating women with NGB and urinary incontinence (UI) will be discussed. Additionally, we will discuss both treatments uniquely applicable to patients with NGB and SUI as well as common treatments that might have unique risks and adaptations in women with NGB. From this review, it is clear that, as standardized practice and technologies continue to grow for management of SUI in patients with comorbid neurological conditions, additional research and analysis may be required to determine the complexities of this unique disease process.

Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but ‘non-stepping’) and robot assisted treadmill trained (but ‘non-stepping’) and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with stepping longer or less successful.

Lipopolysaccharide preconditioning attenuates apoptotic processes and improves neuropathologic changes after spinal cord injury in rats

We have shown earlier that administration of low-dose lipopolysaccharide (LPS) significantly contributed to recovery of motor function after traumatic spinal cord injury in the adult female rat. Using the same standardized animal model, we have now designed a set of experiments to test the hypothesis that LPS preconditioning attenuates stress-related apoptotic processes early after spinal cord trauma. The lower thoracic spinal cord injury in adult female Sprague-Dawley rats was caused by a 10 g weight rod drop from 25 mm on the dural surface of the exposed spinal cord at T10. The rats were randomly assigned to three groups: Sham injury, control (received normal saline alone), and LPS preconditioning (0.2 mg/kg, ip; 72 h prior to the injury). The animals were euthanized at 72 h postinjury. Neuropathologic changes were assessed using hematoxylin and eosin staining. SCI-induced apoptosis were observed by transmission electron microscopy. Caspase-3, cleaved caspase-3, Bax, and Bcl-2 were examined with immunohistochemistry or Western blotting. Compared with the control group, LPS preconditioning group showed significant improvement in the SCI-induced morphology changes. Furthermore, LPS preconditioning reduced the expressions of apoptotic markers caspase-3, cleaved caspase-3, and Bax, upregulated the expression of antiapoptotic marker Bcl-2 in the samples of spinal cord. Low-dose LPS attenuated the recruitment of inflammatory cells and the proliferation of glial cells in the site of injury. LPS preconditioning has neuroprotective effects against TSCI in rats due to its antiapoptosis properties as shown by the inhibition of caspase pathway and the upregulation of antiapoptotic protein.

Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury

Traumatic spinal cord injury (SCI) triggers a systemic inflammatory response (SIR) that contributes to a high incidence of secondary organ complications, particularly after a cervical or high-level thoracic injury. Because liver plays a key role in initiating and propagating the SIR, the aim of this study was to assess the effects that SCI at differing segmental levels has on the intensity of the inflammatory response in the liver. Using male Wistar rats, clip compression SCI was performed at the 4th thoracic (T4 SCI; high-level SCI) or the 12th thoracic (T12 SCI; low-level SCI) spinal cord segment. Sham-injured rats had a partial laminectomy, but no SCI. Leukocyte recruitment to the liver, hepatic blood flow, and hepatocellular injury/death were assessed using intravital microscopy and histology. Chemokine and cytokine concentrations were assessed in the liver. Outcomes were measured at 1.5 hours, 12 hours, and 24 hours after SCI. At 12 hours after injury, T4 SCI caused a threefold increase in hepatic leukocyte recruitment compared with T12 SCI (p < 0.05). T4 SCI induced 50% more hepatocyte injury than T12 SCI at 12 hours (p < 0.05). Hepatic blood flow decreased after SCI, but not after sham injury, and stayed decreased only after T4 SCI at 24 hours after injury. The T4 SCI-induced changes were accompanied by increases in the hepatic concentrations of interleukin-1β, leptin, interleukin 10, and cytokine-induced neutrophil chemoattractant-1 at 1.5 hours. Our findings indicate that traumatic SCI triggers an acute SIR that contributes to hepatocellular injury. SCI-induced remote injury/dysfunction to the liver appears to be transient and is more robust after an upper thoracic SCI compared with a lower thoracic SCI.