Muscle after spinal cord injury

The morphological and contractile changes of muscles below the level of the lesion after spinal cord injury (SCI) are dramatic. In humans with SCI, a fiber‐type transformation away from type I begins 4–7 months post‐SCI and reaches a new steady state with predominantly fast glycolytic IIX fibers years after the injury. There is a progressive drop in the proportion of slow myosin heavy chain (MHC) isoform fibers and a rise in the proportion of fibers that coexpress both the fast and slow MHC isoforms. The oxidative enzymatic activity starts to decline after the first few months post‐SCI. Muscles from individuals with chronic SCI show less resistance to fatigue, and the speed‐related contractile properties change, becoming faster. These findings are also present in animals. Future studies should longitudinally examine changes in muscles from early SCI until steady state is reached in order to determine optimal training protocols for maintaining skeletal muscle after paralysis. Muscle Nerve, 2009     

Reflex effects of induced muscle contraction in normal and spinal cord injured subjects

The modulation of the soleus H reflex in response to functional electrical stimulation (FES) of the rectus femoris (RF) muscle and its overlying skin was examined in 11 normal adults and 6 patients with a clinically defined complete spinal cord injury (SCI). Stimulation of RF at twice motor threshold (MT) resulted in a long-lasting (>1,000 ms) and significant reduction (50-70% of control) in the size of the soleus H reflex in all normal subjects tested. For five of the SCI subjects, 2MT stimulation of RF induced a 55-60% reduction in the soleus H reflex that was also long-lasting (>160 ms). In the remaining SCI subject, 2MT stimulation resulted in an initial period of significant H-reflex facilitation (0-14 ms) that was followed by a longer-lasting inhibition commencing 60 ms after the cessation of the conditioning stimulation. Decreasing the strength of stimulation to below that required to generate a clear contraction in RF resulted in mixed facilitatory and inhibitory actions that were subject dependent. The changes in H-reflex excitability resulting from FES highlight the potential use of FES in the management of hypertonicity in SCI but also suggest that the central actions of FES need to be considered when FES gait restoration programs are designed.     

Sensory perception in complete spinal cord injury

OBJECTIVES: To describe sensations evoked by painful or repetitive stimulation below injury level in patients with a clinically complete (American Spinal Injury Association, ASIA Grade A) spinal cord injury (SCI). MATERIAL AND METHODS: Twenty-four patients (11 with central neuropathic pain and 13 without pain) with a traumatic SCI above the tenth thoracic vertebra were examined using quantitative sensory testing, MR imaging, and somatosensory evoked potentials (SEP). RESULTS: Painful (pressure, pinch, heat or cold) or repetitive (pinprick) stimuli elicited vague localized sensations in 12 patients (50%). Pain, spasticity, and spasms were equally seen in SCI patients with or without localized sensations. SEP and MRI did not differentiate between these two groups. CONCLUSION: The present study suggests retained sensory communication across the injury in complete SCI, i.e. 'sensory discomplete' SCI.     

Monoaminergic and catecholaminergic activation of the central pattern generator for locomotion following spinal cord injury

The development of secondary health complications following spinal cord injury has been increasingly recognized by healthcare professionals as a major concern. These problems most specifically affect complete or near-complete spinal cord injury patients （e.g., those with minimal mobility）, who are not typically rehabilitated with treadmill training approaches, because motor control and leg movements are largely impaired. However, recent pharmaceutical advances in central pattern generator activation may provide new therapeutic hopes for these spinal cord injury patients. This article provides a comprehensive overview, for the non-specialist, of the most recent advances in this field.     

Spontaneous motor unit behavior in human thenar muscles after spinal cord injury.

Our first aim was to characterize spontaneous motor unit activity in thenar muscles influenced by chronic cervical spinal cord injury. Thenar surface electromyography (EMG), intramuscular EMG, and abduction and flexion forces were recorded. Subjects were instructed to relax for 2 min. Units still firing after 10 s were considered spontaneously active. Two distinct patterns of spontaneous unit activity were recorded. Units either fired tonically at a mean frequency of 6.1 HZ or were active sporadically (2.2 HZ). Stimuli (e.g., light touch of nearby skin) were then used to influence tonic spontaneous unit activity. Most stimuli produced a change in firing frequency, usually a temporary increase, but sometimes unit frequency decreased or new activity was initiated. Inputs to these motoneurons clearly make important contributions to changes in unit activity. However, the difficulty that subjects had in stopping unit activity, and the initiation of activity when subjects relaxed, suggest that the source of spontaneity may be the motoneuron itself.     

Estimate of motor conduction in human spinal cord: slowed conduction in spinal cord injury

By using motor evoked potential (MEP) created by transcranial electric stimulation over the motor cortex and F-wave measurement from the peripheral nerve stimulation, it is possible to estimate the spinal cord motor conduction velocity (SCMCV) in the diseased state. Twenty-four patients with spinal cord injury (SCI) between T1 and T11 neurological levels participated in this study. MEP in leg muscle was absent in all neurologically complete paraplegics. In 16 patients with neurologically incomplete SCI, MEP was obtained in 13 patients. The SCMCV estimated from C7 to T12 spinal levels was 32.1 (SD = 9.4) m/s. This was significantly slower than 63.3 (SD = 8.6) m/s in 40 normal controls. This noninvasive, indirect method is measurable, and can provide valuable electrophysiological data in the assessment of motor function in patients with SCI.     

Changes in metabotropic glutamate receptor expression following spinal cord injury

Spinal cord injury (SCI) initiates biochemical events that lead to an increase in extracellular excitatory amino acid concentrations, resulting in glutamate receptor-mediated excitotoxic events. These receptors include the three groups of metabotropic glutamate receptors (mGluRs). Group I mGluR activation can initiate a number of intracellular pathways that increase neuronal excitability. Group II and III mGluRs may function as autoreceptors to modulate neurotransmission. Thus, all three groups may contribute to the mechanisms of central sensitization and chronic central pain. To begin evaluating mGluRs in SCI, we quantified the changes in mGluR expression after SCI in control (naive), sham, and impact injured adult male Sprague-Dawley rats (200-250 g). SCI was produced at spinal segment T10 with a New York University impactor (12.5-mm drop, 10-g rod of 2-mm diameter). Expression levels were determined by Western blot and immunohistochemistry analyses at the epicenter of injury, as well as segments rostral and caudal. The group I subtype mGluR1 was increased over control levels in segments rostral and caudal by postsurgical day (PSD) 7 and remained elevated through PSD 60. The group I subtype mGluR5 was unchanged in all segments rostral and caudal to the injury at every time point measured. Group II mGluRs were decreased compared to control levels from PSD 7 through PSD 60 in all segments. These results suggest that different subtypes of mGluRs have different spatial and temporal expression patterns following SCI. The expression changes in mGluRs parallel the development of mechanical allodynia and thermal hyperalgesia following SCI; therefore, understanding the expression of mGluRs after SCI may give insight into mechanisms underlying the development of chronic central pain.     

Discharge properties of single motor units in patients with spinal cord injuries

To study neurophysiological correlates of spastic paresis, we analyzed the discharge pattern of single motor units (SMUs) during sustained voluntary contraction from muscles weakened by spinal cord injury (SCI) and from muscle of near normal strength just at or above the level of injury., The average firing rate of SMUs was reduced in patients' biceps brachii and tibialis anterior muscles compared with controls, but not in the triceps brachii. Floating serial correlation coefficients obtained form successive interdischarge intervals were significantly more positive in patients than in controls in all three muscles. One statistical measure of regularity of discharge, akin to a coefficient of variation, was best able to differentiate patient and control SMUs. Increased discharge variability in muscle just above the level of injury suggested that subtle effects of traumatic SCIs were more extended than was clinically apparent. Although consistent statistical differences could be measured, these changes were not specific to SCI, nor were all SMUs equally affected. © 1993 John Wiley & Sons, Inc.     

脊髓损伤的移植治疗进展

脊髓损伤的治疗是神经科学领域的难点热点问题之一。本以神经干细胞移植为重点综述了脊髓损伤的多种移植治疗方案及其治疗效果。并对比不同治疗方案的优缺点阐述了应用于临床治疗的可能性。     

不同类型脊髓损伤患者和正常成人外周血白细胞糖皮质激素受体的比较及意义

目的 比较正常成人和急性脊髓损伤患者、慢性脊髓压迫症患者外周血白细胞塘皮质激素受体的结合位点数并探讨其意义。方法 采用放射配体结合法测定15例正常成人、20例急性脊髓损伤患者和21例慢性脊髓压迫症患者外周血白细胞上糖皮质激素受体结合位点数。结果 正常成人外周血白细胞精皮质激素受体结合位点数为4462±891.6个/细胞,慢性脊髓压迫症患者为4225±1271个/细胞,急性脊髓损伤患者为2517±857.8个/细胞,经统计学比较正常成人组和慢性脊髓压迫症患者组没有显著性差异,急性脊髓损伤组与其他两者相差均有显著性意义。急性脊髓损伤组中,全瘫患者为2279±921个/细胞,不全瘫患者为2806±718个/细胞,两者无统计学差异。结论 外周血白细胞上的糖皮质激素受体有高亲和力和低亲和力两种结合位点,急性脊髓损伤后外周血白细胞的精皮质激素受体结合位点数的减少主要是高亲和力位点的减少,低亲和力位点维持不变。大剂量的糖皮质激素和白细胞的低亲和力位点结合,抑制白细胞的趋向移动,减少白细胞进入损伤脊髓区,减轻损伤后的急性炎症反直,起到神经保护作用。慢性脊髓压迫症患者予以糖皮质激素治疗无疗效。     

Serum albumin improves recovery from spinal cord injury

A neuroprotective factor is shown to be present in mammalian serum. This factor is identified by Western blotting to be serum albumin. The serum factor and albumin both protected cultured spinal cord neurons against the toxicity of glutamate. The inability of K252a, a blocker of the high affinity tyrosine kinase receptor for members of the nerve growth factor family, to block the neuroprotective effect of the serum factor established that the serum factor is not a member of the nerve growth factor family. Post-injury injection of albumin intravenously or into the site of injury immediately after injury both improved significantly locomotor function according to Basso-Beattie-Bresnahan assessment and spontaneous locomotor activity recorded with a photobeam activity system. Albumin has multiple mechanisms whereby it may be neuroprotective, and it is a potentially useful agent for treating neurotraumas.     

The glial scar in spinal cord injury and repair

Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCI) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI.     

Role of group II and group III metabotropic glutamate receptors in spinal cord injury.

Spinal cord injury (SCI) produces an increase in extracellular excitatory amino acid (EAA) concentrations that results in glutamate receptor-mediated excitotoxic events. An important class of these receptors is the metabotropic glutamate receptors (mGluRs). mGluRs can activate a number of intracellular pathways that increase neuronal excitability and modulate neurotransmission. Group I mGluRs are known to modulate EAA release and the development of chronic central pain (CCP) following SCI; however, the role of group II and III mGluRs remains unclear. To begin evaluating group II and III mGluRs in SCI, we administered the specific agonists for group II, APDC, or group III, L-AP4, by interspinal injection immediately following SCI. Contusion injury was produced at spinal segment T10 with a New York University impactor (12.5-mm drop, 10-g rod 2 mm in diameter) in 30 adult male Sprague-Dawley rats (175-200 g). Evoked and spontaneous behavioral measures of CCP, locomotor recovery, changes in mGluR expression, and amount of spared tissue were examined. Neither APDC nor L-AP4 affected locomotor recovery or the development of thermal hyperalgesia; however, L-AP4 and APDC attenuated changes in mechanical thresholds and changes in exploratory behavior indicative of CCP. APDC- and L-AP4-treated groups had higher expression levels of mGluR2/3 at the epicenter of injury on post contusion day 28; however, there was no difference in the amount of spared tissue between treatment groups. These results demonstrate that treatment with agonists to group II and III mGluRs following SCI affects mechanical responses, exploratory behavior, and mGluR2/3 expression without affecting the amount of tissue spared, suggesting that the level of mGluR expression after SCI may modulate nociceptive responses.     

How does the human brain deal with a spinal cord injury?

The primary sensorimotor cortex of the adult brain is capable of significant reorganization of topographic maps after deafferentation and de-efferentation. Here we show that patients with spinal cord injury exhibit extensive changes in the activation of cortical and subcortical brain areas during hand movements, irrespective of normal (paraplegic) or impaired (tetraplegic patients) hand function. Positron emission tomography ([¹⁵O]-H₂O-PET) revealed not only an expansion of the cortical ‘hand area’ towards the cortical ‘leg area’, but also an enhanced bilateral activation of the thalamus and cerebellum. The areas of the brain which were activated were qualitatively the same in both paraplegic and tetraplegic patients, but differed quantitatively as a function of the level of their spinal cord injury. We postulate that the changes in brain activation following spinal cord injury may reflect an adaptation of hand movement to a new body reference scheme secondary to a reduced and altered spino-thalamic and spino-cerebellar input.     

Exaggerated auditory startle responses in patients with spinal cord injury

OBJECTIVE: Central nervous system reorganization following spinal cord injury (SCI) may cause functional changes in the motor tracts in patients in whom increased auditory startle responses (ASRs) have been previously reported. We hypothesized that if increased ASRs in patients with incomplete SCI were due to compensatory mechanisms, these changes would be related to severity and/or localization of the lesion. METHODS: We examined ASR characteristics in 29 SCI patients and 14 age-matched healthy volunteers. Fourteen patients had incomplete and 15 complete SCI; 10 patients had cervical and 19 thoracolumbar SCI. Five auditory stimuli were applied binaurally to subjects in a sitting position, with a 5-min interstimulus interval. Surface electromyographic recordings were obtained from orbicularis oculi (OOc), sternocleidomastoid (SCM), biceps brachii (BB), and tibialis anterior (TA) muscles. RESULTS: ASR probability was significantly higher and area-under-the-curve was significantly larger in SCM and BB in patients than in controls. ASR latency was significantly shorter in SCM and BB in patients with cervical than in those with thoracolumbar SCI (p < 0.02), but there were no statistically significant differences between complete and incomplete SCI (p > 0.1). Time span since onset correlated significantly with ASR area in OOc, SCM and BB (p < 0.05). CONCLUSION: The capability of the adult central nervous system to reorganize its circuits over time for improved functionality following injury is probably the key to understanding the increased ASRs in patients with SCI. The exaggeration of the startle reflex is potentially important since it may be useful for augmenting voluntary movement in the clinical rehabilitation of patients with SCI.     

The translational importance of establishing biomarkers of human spinal cord injury

The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging. Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable. Furthermore, the difficulty in predicting neu-rologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power. Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research. As such, the objective of the present review was to de-scribe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood. We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neuro-logical outcome.     

Ion channel blockers and spinal cord injury

The activation of a delayed secondary cascade of unsatisfactory cellular and molecular responses after a primary mechanical insult to the spinal cord causes the progressive degeneration of this structure. Disturbance of ionic homeostasis is part of the secondary injury process and plays an integral role in the early stage of spinal cord injury (SCI). The secondary pathology of SCI is complex and involves disturbance of the homeostasis of K(+) , Na(+) , and Ca(2+) . The effect of ion channel blockers on chronic SCI has also been proved. In this Mini-Review, we provide a comprehensive summary of the effects of ion channel blockers on the natural responses after SCI. Combination therapy is based on the roles of ions and disturbance of their homeostasis in SCI. The effects of ion channel blockers suggest that they have potential in the treatment of SCI, although the complexity of their effects shows that further knowledge is needed before they can be applied clinically.     

人参皂甙对损伤脊髓诱发电位的影响

目的　研究猫急性脊髓损伤 (SCI)后脊髓诱发电位 (SCEP)的变化规律及人参皂甙 (GS)对其的影响 ,探讨 GS对 SCI的作用 ,旨在寻求治疗 SCI的新方法。方法　采用改良 Allen氏重量打击法制作猫急性脊髓损伤模型 ,动物随机分组 ,通过电生理及病理学方法 ,研究 SCEP的变化规律及 GS对其的影响 ,脊髓形态学的改变作为进一步的佐证。结果　 (1)损伤组伤后 SCEP辐值随时间延长逐渐变小 ,潜伏期逐渐延长 ;治疗组波形则逐渐恢复 ,6 h全部恢复 ,差异显著。(2 )光镜下两组均有水肿、中心性出血 ,神经元空泡变性 ,核溶解或固缩 ,尼氏小体消失 ,部分神经纤维脱髓鞘或断裂 ,损伤组最重 ,治疗组均有不同程度的恢复。结论　 GS对 SCI有治疗作用。