Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.     

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.     

电针刺激脊髓损伤患者穴位的脊髓磁共振功能成像激活区特征****☆

背景：研究发现脊髓功能激活区域和电生理等理论对应区域相一致,多数学者认为使用功能磁共振技术检测脊髓神经功能是可行的。 目的：检测电针刺激脊髓损伤患者的脊髓磁共振功能成像激活区特征,验证使用脊髓磁共振功能成像技术来客观评价针灸治疗脊髓损伤疗效的可行性。 方法：使用电针同时刺激3例脊髓损伤患者和5名健康志愿者的右手合谷穴和曲池穴,采用组块设计方法,使用SPM2软件得到患者和健康志愿者脊髓内真实的激活区,分析激活区在矢状位和横断位上的分布特征,并与健康志愿者的激活分布对比,找出患者的激活分布差异。 结果与结论：5名健康志愿者在脊柱C2、C5段均重复出现激活信号,在C6段4名出现激活;3例脊髓损伤患者在脊柱C2,C6段均出现均重复出现激活,其中1例患者与健康志愿者激活分布特征基本一致。可以观察到针灸刺激脊髓损伤患者的脊髓功能激活,因此可以根据功能激活区的分布及强度,在一定程度上客观评价针灸治疗脊髓损伤的疗效。 关键词：磁共振功能成像;脊髓损伤;针灸;穴位;SEEP;数字化图像与影像     

Protective effects of gonadal hormones on spinal motoneurons following spinal cord injury

Spinal cord injury(SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI. We previously demonstrated that motoneurons, and the muscles they innervate, show pronounced atrophy after SCI. Importantly, SCI-induced atrophy of motoneuron dendrites can be attenuated by treatment with gonadal hormones, testosterone and its active metabolites, estradiol and dihydrotestosterone. Similarly, SCI-induced reductions in muscle fiber cross-sectional areas can be prevented by treatment with androgens. Together, these findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be ameliorated by treatment with gonadal hormones, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.     

Ischemia of the anterior horn of the spinal cord

Ischemia of the motoneurons in the anterior horn is a well known pathological entity. Their clinical signs and symptoms are similar to those of amyotrophic lateral sclerosis. Evidence by selective angiography of angiomas of the spinal cord or compression or deviation of Adamkiewicz artery may be suggestive of an initial vascular lesion. Various data (knowledge of development or lesions during experimental ischemia, selective electrophysiologic analysis of anterior horn neurons, evidence of precise circumstances of spinal vascular disorder or spinal arteriography) suggest that anterior horn ischemia is a multiple aspect phenomenon. Our 4 cases illustrate this hypothesis and demonstrate under confirmed vascular circumstances the different clinical aspects of anterior horn ischemic lesions. In addition to typical amyotrophic paralysis unusual or misleading symptoms may occur such as claudication, paroxysmal contractures or progressive spastic paraparesis. Investigations required and possible treatment of the lesions are simplified by awareness of these various clinical aspects.     

Substance pin spinal cord dorsal horn decreases following peripheral nerve injury

Substance P was located in the spinal cord of rats by immunocytochemistry.Section and ligation of the sciatic nerve produced a depleted area low in substance P in the medial two-thirds of laminae 1 and 2 of segments L4 and 5.The time of depletion began about 5 days after the nerve had been cut and substance P reached a steady minimum by about 9 days and remained depleted for the entire period examined, 31 days.Crush lesions of the sciatic nerve failed to produce the marked and rapid changes of spinal cord substance P observed after section and ligation.     

An update on functional electrical stimulation after spinal cord injury

Recent advances in biomedical engineering as applied to neurologic rehabilitation have finally borne clinically relevant fruit. Nowhere is this more evident than in the field of functional electrical stimulation (FES). This article highlights the remarkable clinical progress that has been made in the use of electrical stimulation for restoring movement and function in individuals with spinal cord injury. Specific attention is given to respiratory-assist devices, hand-grasp systems, standing and walking, and bladder control. This review article features discussion of eight devices that have gone through the United States Food and Drug Administration (FDA) regulatory approval process.     

Effect of load during electrical stimulation training in spinal cord injury

Electrical stimulation training is known to alter skeletal muscle characteristics after a spinal cord injury, but the effect of load on optimizing the training protocol has not been fully investigated. This study investigated two electrical-stimulation training regimes with different loads on intramuscular parameters of the paralyzed lower limbs. Six paraplegic individuals with a spinal cord injury underwent electrical stimulation training (45 min daily for 3 days per week for 10 weeks). One leg was trained statically with load, and the contralateral leg was trained dynamically with minimal load. Isometric force assessed with 35-HZ stimuli increased significantly in both legs from baseline, with the static-trained leg also being significantly higher than the dynamic-trained leg. The vastus lateralis muscle of the statically trained leg showed a significant increase in type I fibers, fiber cross-sectional area, capillary-to-fiber ratio, and citrate synthase activity when compared to both baseline and the dynamically trained leg. Relative oxygenation of the vastus lateralis muscle as determined by near infrared spectroscopy was also significantly greater after static training. This study indicates that the load that is applied to paralyzed muscle during an electrical stimulation training program is an important factor in determining the amount of muscle adaptation that can be achieved.     

Scapulo-peroneal muscular atrophy. Full autopsy report. Unusual findings in the anterior horn of the spinal cord. Lipid storage in muscle

Morphological findings of 3 cases of Kaeser's scapulo-peroneal muscular atrophy are described. 1 of them is the first complete autopsy report on this disease. While the number of motor neurons in the spinal cord was grossly normal, the neuropil of the anterior horn exhibited axonal swellings, accumulations of possibly pathological lipofuscin and intra-axonal corpora amylacea. In the muscles, changes were partly those of neurogenic atrophy, partly of a primary myopathy. There was also an accumulation of neutral fat in the muscle fibres, mainly of those of type I.     

Depression and recovery of reflex amplitude during electrical stimulation after spinal cord injury

ObjectiveThe aim of this study was to quantify, for the first time, H-reflexes evoked during prolonged trains of wide-pulse neuromuscular electrical stimulation (WP-NMES) in individuals with chronic spinal cord injury (SCI). We hypothesised that after the first H-reflex, reflex amplitudes would be depressed (due to post-activation depression), but would recover and this recovery would be enhanced after a “burst” of 100 Hz WP-NMES.MethodsSoleus M-waves and H-reflexes evoked during WP-NMES (1 ms pulse width) of the tibial nerve were quantified in nine individuals with SCI. WP-NMES was delivered in two patterns: “constant-frequency” (15 or 20 Hz for 12 s) and “burst-like” (15-100-15 Hz or 20-100-20 Hz; 4 s each phase) at an intensity that evoked an M-wave between 10% and 15% of the maximal M-wave (M_max).ResultsDuring constant frequency stimulation, after the initial depression from the first to the second H-reflex (1st: 57% M_max; 2nd: 25% M_max), H-reflexes did not recover significantly and were 37% M_max at the end of the stimulus train. During the burst-like pattern, after the initial depression (1st: 62% M_max; 2nd: 30%), reflexes recovered completely by the end of the stimulation (to 55% M_max) as they were not significantly different from the first H-reflex. M-waves were initially depressed (1st: 12% M_max; 2nd: 7% M_max) then did not change throughout the stimulation and were not significantly different between stimulation patterns. An analysis of covariance indicated that the depression in M-wave amplitude did not account for the depression in H-reflex amplitude.ConclusionsRelatively large H-reflexes were recorded during both patterns of NMES. The brief burst of 100 Hz stimulation restored H-reflexes to their initial amplitudes, effectively reversing the effects of post-activation depression.SignificanceFor individuals with chronic SCI, generating contractions through central pathways may help reduce muscle atrophy and produce contractions that are more fatigue-resistant for rehabilitation, exercise programs, or to perform activities of daily living.     

Apelin inhibits motor neuron apoptosis in the anterior horn following acute spinal cord and sciatic nerve injuries

Rat models of acute spinal cord injury and sciatic nerve injury were established.Apelin expression in spinal cord tissue was determined.In normal rat spinal cords,apelin expression was visible;however,2 hours post spinal cord injury,apelin expression peaked.Apelin expression increased 1 day post ligation of the sciatic nerve compared with normal rat spinal cords,and peaked at 3 days.Apelin expression was greater in the posterior horn compared with the anterior horn at each time point when compared with the normal group.The onset of neuronal apoptosis was significantly delayed following injection of apelin protein at the stump of the sciatic nerve,and the number of apoptotic cells after injury was reduced when compared with normal spinal cords.Our results indicate that apelin is expressed in the normal spinal cord and central nervous system after peripheral nerve injury.Apelin protein can reduce motor neuron apoptosis in the spinal cord anterior horn and delay the onset of apoptosis.     

局部缺血坐骨神经相关神经元胞体乙酰胆碱酯酶变化的定量分析

BACKGROUND： Peripheral nerve ischemia has been shown to result in ischemic fiber degenera-tion and axoplasmic transport disturbance. However, the effect on acetylcholinesterase （AChE） ex- pression in relevant cells following sciatic nerve ischemia remains unclear.
OBJECTIVE： To observe AChE concentration changes following peripheral nerve ischemia.
DESIGN, TIME AND SETTING： The present comparative observation, neuroanatomical experiment was performed at the Central Laboratory Animal of Chengde Medical College between 2006 and 2007.
MATERIALS： A total of 20 healthy, adult, Wistar rats were randomized into two groups （n = 10）： 8-day ischemia and 14-day ischemia.
METHODS： Ischemia injury was induced in the unilateral sciatic nerve （experimental side） through ligation of the common iliac artery. The contralateral side received no intervention, and served as the control side. Rats in the 8-day ischemia and 14-day ischemia groups were allowed to survive for 8 and 14 days, respectively.
MAIN OUTCOME MEASURES： The L5 lumbar spinal cord and the L5 dorsal root ganglion were removed from both sides and sectioned utilizing a Leica vibrating slicer. AChE cellular expression was detected using Karnovsky-Root, and the number of AChE-positive cells and average gray value were analyzed using a MiVnt image analysis system.
RESULTS： In the 8-day ischemia group, AChE-positive cell numbers were significantly less in the dorsal root ganglion and spinal cord anterior horn of the experimental side, but the average gray value was significantly greater, compared with the control side （P 〈 0.05）. These changes were more significant in the 14-day ischemia group than in the 8-day ischemia group （P 〈 0.01）.
CONCLUSION： Peripheral nerve ischemia leads to decreased AChE expression in the associated cells in a time-dependent manner.     

Disuse muscle atrophy exacerbates motor neuronal degeneration caudal to the site of spinal cord injury

Spinal cord injury is often followed by disuse muscle atrophy. The effect of disuse muscle atrophy on motor neurons below the level of spinal cord lesions is not fully understood. We produced spinal contusions in the mid-thoracic segment (Th7/8) of rats. To promote disuse muscle atrophy, their hind limbs were immobilized. Alpha-motor neurons in L4/5 at 3 weeks postinjury showed signs of degeneration associated with disuse muscle atrophy. Muscle atrophy alone did not produce a significant α-motor neuronal degeneration. Our results demonstrate that disuse muscle atrophy within the context of spinal cord injury exacerbates motor neuronal degeneration in caudal regions remote from the injury.