Cystometrographic patterns in predicting bladder function after spinal cord injury

The cystometrographic patterns together with and sphincter electromyograms of 62 patients with recent spinal cord injury wer analysed. Four main patterns could be distinguished. The patients with well-developed detrusor reflex gained easy emptying of the bladder significantly more often than those with supranuclear injury but weak or unsustained detrusor contractions, or those with mixed spinal lesions. The patients with mixed lesions and low compliance bladders had the most severe incontinence problems. One fourth of the total series had various degrees of upper tract dilatation in their first urogram, and these changes occurred more often in patients with high detrusor activity. Urinary tract infections occurred in all patients but less often in those with areflexic bladders. This group of patients was also most suitable for intermittent self-catheterisation.     

Targeting the motor cortex to restore walking after incomplete spinal cord injury

Spinal cord injury(SCI),second only to stroke,is the leading cause of paralysis.The ability to walk is often lost after SCI,reducing independence and quality of life.Restoration of walking is cited as a priority among persons with SCI of all degrees of severity,chronicity,or age at injury.As 70%of SCIs are anatomically incomplete,some neural connections relaying information to and from the brain are spared.     

Multi-system neurorehabilitative strategies to restore motor functions following severe spinal cord injury

Severe spinal cord injury (SCI) permanently abolishes motor functions caudal to the lesion. However, the neuronal machinery sufficient to produce standing and stepping is located below most SCI, and can be reactivated with training. Therefore, why do rats and humans fail to regain significant levels of motor control after a severe SCI? In this review, we argue that the lack of sustainable excitability in locomotor circuitries after SCI prevents the emergence of functional motor states during training, thus limiting the occurrence of activity-dependent plasticity in paralyzed subjects. In turn, we show that spinal rats trained with combinations of epidural electrical stimulation and monoamine agonists, which promote locomotor permissive states during rehabilitation, can regain coordinated stepping with full weight bearing capacities in the total absence of supraspinal influences. This impressive recovery of function relies on the ability of spinal circuitries to utilize multisensory information as a source of control and learning after the loss of brain input. We finally discuss the implication of these findings for the design of multi-system neurorehabilitative interventions capable of restoring some degree of function in humans with severe SCI.     

Inflammation-induced GDNF improves locomotor function after spinal cord injury

Activation of microglia/macrophages after injury occurs limitedly in the CNS, which finding may explain unsuccessful axonal regeneration. Therefore, the relationship between lipopolysaccharide (LPS)-induced inflammation and recovery of locomotor function of rats after spinal cord injury was examined. High-dose LPS improved locomotor function greater than low-dose LPS, being consistent with the expression of neurotrophic factor (GDNF) in microglia/macrophages. Experiments using GDNF gene mutant mice confirmed that the increase in the GDNF mRNA level, rather than the reduction in the mRNA level of inducible NO synthase, could be correlated with the restoration activity of locomotor function. These results suggest that a higher degree of inflammation leads to a higher degree of repair of CNS injuries through GDNF produced by activated microglia/macrophages.     

Bexarotene improves motor function after spinal cord injury in mice

Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system. Therefore, early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury. Bexarotene, a type of retinoid, exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson’s disease. Bexarotene has been proven to promote autophagy, but it has not been used in the treatment of spinal cord injury. To investigate the ...     

Passive exercise and fetal spinal cord transplant both help to restore motoneuronal properties after spinal cord transection in rats

Spinal cord transection influences the properties of motoneurons and muscles below the lesion, but the effects of interventions that conserve muscle mass of the paralyzed limbs on these motoneuronal changes are unknown. We examined the electrophysiological properties of rat lumbar motoneurons following spinal cord transection, and the effects of two interventions shown previously to significantly attenuate the associated hindlimb muscle atrophy. Adult rats receiving a complete thoracic spinal cord transection (T-10) were divided into three groups receiving: (1) no further treatment; (2) passive cycling exercise for 5 days/week; or (3) acute transplantation of fetal spinal cord tissue. Intracellular recording of motoneurons was carried out 4-5 weeks following transection. Transection led to a significant change in the rhythmic firing patterns of motoneurons in response to injected currents, as well as a decrease in the resting membrane potential and spike trigger level. Transplants of fetal tissue and cycling exercise each attenuated these changes, the latter having a stronger effect on maintenance of motoneuron properties, coinciding with the reported maintenance of structural and biochemical features of hindlimb muscles. The mechanisms by which these distinct treatments affect motoneuron properties remain to be uncovered, but these changes in motoneuron excitability are consistent with influences on ion conductances at or near the initial segment. The results may support a therapeutic role for passive limb manipulation and transplant of stem cells in slowing the deleterious responses of motoneurons to spinal cord injury, such that they remain more viable for subsequent alternative strategies.     

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     

Neurogenic bladder model for spinal cord injury: spinal cord microdialysis and chronic urodynamics

We describe an animal model to study neurotransmitter changes in parallel with urodynamic testing following Spinal Cord Injury (SCI). Urodynamic access was achieved using a subcutaneously placed 7 French dual lumen portacatheter. Spinal cord injury was induced by weight drop technique onto exposed dura at T8. The L6-S1 detrusor nuclei were localized stereotactically and microdialysis probe placement was confirmed through histologic methods. Chronic urodynamics revealed detrusor hyperreflexia (DH) 14 days following SCI. In vivo microdialysis of spinal cord amino acids was performed using CMA 11 (240 uM) probes in halothane-anesthetized rats at baseline and intervals of 20-30 min following spinal cord injury. Significant increases in the excitatory amino acid glutamate, and the inhibitory amino acids, glycine and taurine, were seen following spinal cord injury. Amino acid levels peaked at approximately 40 min following contusion injury with glycine demonstrating the highest levels of all amino acids measured. This neurogenic rat model provides a useful means of examining the effects of spinal cord injury on bladder function. By utilizing spinal cord microdialysis, one could intervene at the level of the detrusor nuclei to modulate bladder function.     

Deficits in bladder function following spinal cord injury vary depending on the level of the injury

Loss of bladder function is an important consequence of a spinal cord injury (SCI) but is rarely assessed in animal studies of SCI. Here, we use a simple outcome measure (volume of retained urine) to assess bladder dysfunction over time following moderate contusion injuries at 3 different thoracic levels (T1, T4, or T9) and complete crush injuries (T1 vs. T9). The volume of urine retained in the bladder was measured daily for fourteen days post injury by anesthetizing the animals with isoflurane, expressing the bladder, and weighing the urine. To compare bladder deficits with the degree of impairment of hindlimb motor function, locomotion was assessed using the BBB open field rating scale. Rats with contusions at T4 and T9 exhibited bladder impairments reflected by increased urine retention from 1 to 12 days post injury. In contrast, rats with contusions at T1 exhibited minimal deficits (smaller volumes of retained urine). Lesion size and overall functional impairment were comparable between groups based on quantitative assessments of lesion area at the epicenter and BBB locomotor scores. Moreover, a sector analysis of sparing of different portions of the white matter revealed no differences in sparing of different funiculi between the groups. Injections of Fluorogold into lumbar segments led to retrograde labeling of a larger number of neurons in the pontine micturition center (PMC) following T1 injury when compared to T4 or T9. Thus, moderate contusion lesions at T1 spare a critical descending pathway able to mediate at least reflex voiding in rats.     

Time representation of mitochondrial morphology and function after acute spinal cord injury

Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.     

Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury

The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes. The effect of microelectrode stimulation was studied under light Propofol anesthesia at monthly intervals for up to 14 months. We found that electrical stimulation in the sacral parasympathetic nucleus at S(2) level or in adjacent ventrolateral white matter produced bladder contractions insufficient for inducing voiding, while stimulation at or immediately dorsal to the dorsal gray commissure at S(1) level produced strong (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg) external urethral sphincter relaxation, resulting in bladder voiding in 14 animals. In a subset of three animals, spinal cord transection was performed. For several months after the transection, intraspinal stimulation continued to be similarly or even more effective in inducing the bladder voiding as before the transection. We speculate that in the absence of the supraspinal connections, the plasticity in the local spinal circuitry played a role in the improved responsiveness to intraspinal stimulation.     

New perspectives on improving upper extremity function after spinal cord injury

Injury to the cervical spinal cord adversely affects arm and hand function to varying degrees depending on the level and severity of injury. These impairments typically result in reduced independence in the performance of activities of daily living and limit participation in recreational activities. There is evidence to suggest individuals with incomplete spinal cord injury may benefit from intensive rehabilitation interventions aimed at improving hand and arm function. Massed practice (repetitive activity-based training) and somatosensory stimulation (prolonged peripheral nerve electrical stimulation at submotor threshold intensity) are 2 interventions that have been shown to improve strength and function in individuals with stroke, presumably by changing cortical excitability. These techniques, however, had not previously been investigated in individuals with spinal cord injury (SCI). In this article the stroke and SCI literature supporting the use of massed practice and somatosensory stimulation as a potential rehabilitative tool to promote recovery of function in individuals with incomplete cervical spinal cord injury (SCI) is reviewed. Recently published research using these novel techniques in which a combination of massed practice and somatosensory stimulation resulted in increased pinch grip strength and upper extremity function in individuals with incomplete cervical SCI when compared to subjects participating in massed practice alone is presented.     

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T(9)-T(10) spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β-methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 μM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (P=0.041). This was accompanied by a substantial decrease in α,β-methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, P=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms.     

Disorders of bladder function in spinal cord disease

Successful management of bladder function mandates a thorough knowledge of the neuroanatomy and physiology of micturition. Accurate urodynamic diagnosis of the exact vesicourethral dysfunction is a key to successful management. The primary concern for the urologist is preservation of renal function, taking into account the social needs of the patient.     

体感诱发电位在脊髓损伤后药物疗效观察中的应用

目的观察大鼠脊髓损伤后药物对体感诱发电位（ＳＥＰ）的影响。方法４８只Ｗｉｓｔａｒ大鼠脊髓损伤术后立即给小檗胺或尼莫地平１次，术后２、４、８小时各给同样药１次，以后每日２次给药，至术后２周。分别于术前及术后４周在麻醉状态下进行ＳＥＰ检查。结果脊髓损伤后４周各组实验动物的ＳＥＰ潜伏期都有一定程度的延长，脊髓传导速度明显下降。大剂量小檗胺组与对照组相比其潜伏期及损伤部位的传导时间均明显缩短，损伤部位的传导速度明显加快，与对照组相比差异有极显著性意义（Ｐ＜０．０１）。结论ＳＥＰ能客观评价脊髓的神经传导功能，对脊髓损伤后药物疗效观察有一定的客观意义。