Locomotion induced by spinal cord stimulation in the neonate rat in vitro.

The present studies employed the neonate rat brain stem-spinal cord preparation to determine whether electrical stimulation of the lumbosacral enlargement (LE) of the spinal cord itself can be used to elicit locomotion, and whether or not such stimulation persists in inducing locomotion following midthoracic spinal cord transection or hindlimb deafferentation. Results suggest that (1) stimulation of the dorsal columns or ventral funiculus of the LE is effective in inducing airstepping in the neonatal rat brain stem-spinal cord limb-attached preparation; (2) central disconnection by midthoracic spinal cord transection does not alter LE-stimulation-induced airstepping and may lead to an increase in stepping frequency if suprathreshold stimulation is used; and (3) dorsal root section also leads to an increase in the frequency of suprathreshold LE-stimulation-induced locomotion, but there is not further increase in frequency if a spinal cord transection is performed in addition to dorsal rhizotomy.     

Interactions between spinal cord stimulation and activity blockade in the regulation of synaptogenesis and motoneuron survival in the chick embryo

The present study investigated the effects of spinal cord stimulation, neuromuscular blockade, or a combination of the two on neuromuscular development both during and after the period of naturally occurring motoneuron death in the chick embryo. Electrical stimulation of the spinal cord was without effect on motoneuron survival, synaptogenesis, or muscle properties. By contrast, activity blockade rescued motoneurons from cell death and altered synaptogenesis. A combination of spinal cord stimulation and activity blockade resulted in a marked increase in motoneuron death, and also altered synaptogenesis similar to that seen with activity blockade alone. Perturbation of normal nerve–muscle interactions by activity blockade may increase the vulnerability of developing motoneurons to excessive excitatory afferent input (spinal cord stimulation) resulting in excitotoxic-induced cell death. © 1993 John Wiley & Sons, Inc.     

Botulinum toxin A inhibits ATP release from bladder urothelium after chronic spinal cord injury

The effects of mechanoreceptor stimulation and subsequent ATP release in spinal cord injured and normal bladders was examined to demonstrate if spinal cord injury (SCI) modulates the basal or evoked release of ATP from bladder urothelium and whether intravesical botulinum toxin A (BTX-A) administration inhibits urothelial ATP release, a measure of sensory nerve activation. A Ussing chamber was used to isolate and separately measure resting and mechanoreceptor evoked (e.g. hypoosmotic stimulation) ATP release from urothelial and serosal sides of the bladder. Following spinal cord injury, resting urothelial release of ATP was ninefold higher than that of normal rats. Botulinum toxin A instillation did not significantly affect the resting release of ATP after spinal cord injury. Evoked ATP release following hypoosmotic stimulation was significantly higher in chronic spinal cord injured compared to normal rat bladders. However, botulinum toxin A treatment markedly reduced ATP release in spinal cord injured bladders by 53% suggesting that ATP release by mechanoreceptor stimulation, as opposed to basal release, occurs by exocytotic mechanisms. In contrast, there was no significant difference in basal or evoked ATP release from bladder serosa following spinal cord injury. Moreover, intravesical instillation of botulinum toxin A did not affect ATP release from the serosal side after spinal cord injury, suggesting that its effects were confined to the urothelial side of the bladder preparation. In summary: (1) increased release of ATP from the urothelium of spinal cord injured bladders may contribute to the development of bladder hyperactivity and, (2) mechanoreceptor stimulated vesicular ATP release, as opposed to basal non-vesicular release of ATP, is significantly inhibited in spinal cord injured bladders by intravesical instillation of botulinum toxin A. These results may have important relevance in our understanding of the mechanisms underlying plasticity of bladder afferent pathways following SCI.     

Change in muscarinic modulation of transmitter release in the rat urinary bladder after spinal cord injury

Muscarinic facilitation of 14C-ACh release from post-ganglionic parasympathetic nerve terminals was studied in bladder strips prepared from spinal intact (SI) and spinal cord transected (SCT) rats. The spinal cord was transected at the lower thoracic spinal segments 3 weeks prior to the experiments. Using non-facilitatory stimulation (2 Hz) the release of ACh in spinal intact rats did not change in the presence of a non-specific muscarinic antagonist, atropine (100 nM), an M(1) specific antagonist (pirenzepine, 50 nM) or an M(1)-M(3) specific antagonist (4-DAMP, 5 nM). However, during a facilitatory stimulation paradigm (10 Hz or 40 Hz, 100 shocks) atropine and pirenzepine, but not 4-DAMP inhibited the release of ACh in bladders from spinal intact rats, indicating an M(1) receptor-mediated facilitation. In spinal cord transected rats, 2 Hz stimulation-induced release was significantly inhibited by atropine or 4-DAMP but not by pirenzepine indicating that a pre-junctional facilitatory mechanism mediated via M(3) muscarinic receptors could be induced by a non-facilitatory stimulation paradigm after spinal injury. In bladders of spinal cord transected rats, 10 Hz stimulation-evoked release of ACh was also inhibited by atropine and 4-DAMP (5 nM) but not by pirenzepine (50 nM). These results indicate that pre-junctional muscarinic receptors at cholinergic nerve endings in the bladder change after chronic spinal cord injury. It appears that low affinity M(1) muscarinic receptors are replaced by high affinity M(3) receptors. This change in modulation of ACh release may partly explain the bladder hyperactivity after chronic spinal cord injury.     

Noninvasive method to control the human spinal locomotor systems

The mechanism of interactions between receptor activation in the musculoskeletal system and stimulation of the spinal cord in the regulation of locomotor behavior was studied in healthy subjects. Afferent stimulation was tested for effect on the patterns of stepping movements induced by percutaneous stimulation of the spinal cord. A combination of percutaneous spinal cord stimulation and vibratory stimulation was shown to increase the amplitude of leg movements. It was demonstrated that vibratory stimulation of limb muscles at a frequency of less than 30 Hz can be used to control involuntary movements elicited by noninvasive stimulation of the spinal cord.     

Spinal cord stimulation as a tool for physiological research

The use of spinal cord stimulation for alleviation of disabilities due to motor neuron lesions has provided the opportunity to explore a new approach to measurement of spinal cord physiology. Externalized leads of epidural electrodes provide the possibility of recording evoked spinal cord activity, while both externalized or implanted leads can be used to study cortical evoked responses and twitches induced by spinal cord stimulation. The use of such electrophysiological techniques can be expected to expand greatly the applicability of the technique for alleviating motor disabilities, through a better definition of the degree, nature and extent of the lesion.     

Respiratory resetting induced by spinal cord stimulation in the cat

Electrical stimulation (50-150 microA, 0.5-ms duration, 3-300 Hz) was performed within three different regions (lateral, ventrolateral, and ventral) of the C2-C3 spinal cord of decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Spinal cord stimulation sites were located by inserting monopolar or bipolar stimulating electrodes either at the dorsolateral sulcus or at least 1 mm medial or lateral to the sulcus. With stimulation at each site, alterations in respiratory rhythm, orthodromic phrenic nerve responses, and antidromic activation of medullary respiratory-modulated neurons were examined. Phrenic nerve responses to cervical spinal cord stimulation consisted of an early excitation (2-4 ms) and/or a late excitation (4-8 ms). Stimulation of the lateral region evoked the greatest amplitude early response and stimulation of the ventrolateral region produced the greatest late excitation. All three stimulus sites elicited antidromic activation of some respiratory-modulated neurons in the dorsal (DRG) and ventral respiratory groups (VRG). The lateral region was the least effective resetting site, and it had the highest incidence of antidromic activation of both DRG and VRG neurons. The ventrolateral region of the cervical spinal cord was the most effective resetting site, but it had the lowest incidence of antidromic activation of DRG respiratory-modulated neurons. In addition, resetting responses were observed with spinal cord stimulation at similar sites in the thoracic and lumbar spinal cord regions thought to be devoid of inspiratory bulbospinal axons.(ABSTRACT TRUNCATED AT 250 WORDS)     

犬脊髓损伤治疗动物模型

目的　建立犬脊髓损伤治疗动物模型 ,为实验研究提供直接的病例材料。方法　人工损伤犬脊髓 ,使用直流电场刺激使脊髓损伤恢复。结果　人工犬脊髓损伤模型建立 ,直流电场刺激治疗可恢复神经功能。结论直流电场刺激在不同时期对犬脊髓再生及功能恢复均有明显促进作用 ,能促进脊髓再生 ,使脊髓通路更快更完善的建立     

Electrical stimulation in multiple sclerosis. Comparison of transcutaneous electrical stimulation and epidural spinal cord stimulation

Forty-nine multiple sclerosis patients with bladder symptoms and/or walking disability were subjected to a therapeutic trial with electrical spinal cord stimulation and transcutaneous electrical stimulation, a second aim being to compare these two treatments. A clear subjective improvement in bladder symptoms was achieved in the majority of the cases, and this was substantiated by objective parameters. In a proportion of cases a more moderate improvement seems to have been achieved in a variety of symptoms. Transcutaneous electrical stimulation seems to be a useful selection procedure for later electrical spinal cord stimulation.     

Regional blood flow changes in response to thermal stimulation of the brain and spinal cord in the Pekin duck

Summary In conscious Pekin ducks, carotid and sciatic blood flows, respiratory rate, core and skin temperatures were measured during selective thermal stimulations of the spinal cord and rostral brain stem in thermoneutral (20 °C) and warm (32 °C) ambient conditions.At thermoneutral ambient temperature selective heating of the spinal cord by 2–3 °C (to 43–44 °C) increased the carotid blood flow by 138% and the sciatic blood flow by 46%. Increase in blood flows was correlated with increased breathing rate and beak and web skin temperatures.Selective cooling of the spinal cord at warm ambient temperatures and panting reduced the blood flow in both arteries and decreased the breathing rate.Heating or cooling of the brain stem showed generally very weak but otherwise similar responses as thermal stimulation of the spinal cord. In one duck out of six there was a marked effect on regional blood flow during brain stimulation.The results show that thermal stimulation of the spinal cord exerts a marked influence on regional blood flow important in thermoregulation, whereas the lower brain stem shows only a weak thermosensitivity, and stimulation caused only small cardiovascular changes of no major consequence in thermoregulation.     

Protein composition and synthesis in the adult mouse spinal cord

Propepties of spinal cord proteins were studied in adult mice subjected to unilateral crush or electrical stimulation of sciatic nerve. The protein composition of spinal tissue was determined using SDS-polyacrylamide gel electrophoresis coupled with subcellular fractionation. Comparisons of mouse spinal cord and brain revealed similarities in the types but differences in the concentrations of myelin associated proteins, nuclear histones and other proteins. Comparisons with sciatic nerve proteins demonstrated differences in types of proteins but similarities in the concentration of myelin proteins and nuclear histones. The short term (<2 hrs.) incorporation of radioactive amino acids into spinal cord proteins revealed heterogeneous rates of incorporation. Neither nerve crush six days prior to testing nor sciatic nerve stimulation had a significant effect on the protein composition or amino acid incorporation rates of spinal cord tissue. These observations suggest that known differences in spinal cord function following alterations in nerve input may be dependent upon different mechanisms than have been found in the brain.     

大鼠脊髓诱发电位与脊髓损伤的关系——Ⅲ.脊髓局部损毁后电位的变化及电位来源分析

本文描述了大鼠脊髓L_1节段后柱、后索、侧索和前角的诱发电位及其损伤后的变化,并观察了切断L_4、L_5脊神经背、腹根与横断高位颈髓对电位的影响,以进行行电位来源分析。结果可见,上述四个区域的诱发电位基本由早反应三相波和晚反应组成。分别电解损毁这些部位后,电位波幅均普遍降低,晚期反应较早反应降低明显。后柱或后索受损对电位影响最大。局部损毁后可见L_1及T_(13)水平的硬膜上电位改变明显,尤其晚反应减弱、波峰平坦。反应时值与潜伏时未见明显改变。切断L_4脊神经背、腹根后、电位基本消失。去大脑对电位未见明显影响。结果表明,刺激坐骨神经诱发的脊髓电位起源于低位腰段传入神经和脊髓内多通路的兴奋传导,在一定程度上受腹根逆行活动的影响,与大脑及脊髓下行传导束活动无直接联系。脊髓诱发电位的幅度与波形改变可作为脊髓损伤的判断指标之一。     

Cortical potentials evoked by epidural stimulation of the cervical and thoracic spinal cord in man

Scalp somatosensory evoked potentials (SEPs) were recorded after electrical stimulation of the spinal cord in humans. Stimulating electrodes were placed at different vertebral levels of the epidural space over the midline of the posterior aspect of the spinal cord. The wave form of the response differed according to the level of the stimulating epidural electrodes. Cervical stimulation elicited an SEP very similar to that produced by stimulation of upper extremity nerves, e.g., bilateral median nerve SEP, but with a shorter latency. Epidural stimulation of the lower thoracic cord elicited an SEP similar to that produced by stimulation of lower extremity nerves. The results of upper thoracic stimulation appeared as a mixed upper and lower extremity type of SEP. The overall amplitudes of SEPs elicited by the epidural stimulation were higher than SEPs elicited by peripheral nerve stimulation. In 4 patients the CV along the spinal cord was calculated from the difference in latencies of the cortical responses to stimulation at two different vertebral levels. The CVs were in the range of 45–65 m/sec. The method was shown to be promising for future study of spinal cord dysfunctions.     

Electrical stimulation of the cervical spinal cord increases cerebral blood flow in humans

Ten patients were studied to determine the effect of spinal cord stimulation on CBF. In 5 patients using a cervical spinal cord stimulator, the stimulation produced a significant increase in CBF in the hemisphere ipsilateral to the induced paresthesia. Thoracic cord stimulation, used by the other 5 patients, had no effect on CBF. Atropine had no effect on the alteration in CBF produced by cervical cord stimulation. Indomethacin, however, partially blocked the effect. These heuristic observations may have implications for the future treatment of cerebrovascular insufficiency in humans.     

Spinal cord-muscle relations: their role in neuro-muscular development in birds

In the present study we focused our attention on the role of spinal cord-muscle interactions in the development of muscle and spinal cord cells. Four experimental approaches were used: 1) muscle fiber-spinal cord co-culture; 2) chronic spinal cord stimulation in chick embryos; 3) direct electrical stimulation of the denervated chick muscle; 4) skeletal muscle transplantation in close apposition to the spinal cord in chick embryos. The characteristics of mATPase and energetic metabolism enzyme activities and of myosin isoform expression were used as markers for fiber types in two peculiar muscles, the fast-twitch PLD and the slow-tonic ALD. In vitro, in the absence of neurons, myoblasts can express some characteristics of either slow or fast muscle types according to their origin, while in the presence of neurons, muscle fiber differentiation seems to be related to the spontaneous rhythm delivered by the neurons. The in ovo experiments of chronic spinal cord stimulation demonstrate that the differentiation of the fast and slow muscle features appears to be rhythm dependent. In the chick, direct stimulation of denervated muscles shows that the rhythm of the muscle activity is also involved in the control of muscle properties. In chick embryos developing ALD, the changes induced by modifications of muscle tension demonstrate that this factor also influences muscle development. Other experiments show that muscle back-transplantation can alter the early spinal cord development.     

Intracranial Somatosensory Responses with Direct Spinal Cord Stimulation in Anesthetized Sheep

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.     

Locomotion induced by epidural stimulation in a decerebrated cat after spinal cord injury

The effect of partial and complete spinal cord transection (Th7–Th8) on locomotor activity evoked in decerebrated cats by electrical epidural stimulation (segment L5, 80–100 μA, 0.5 ms at 5 Hz) has been investigated. Transection of dorsal columns did not substantially influence the locomotion. Disruption of the ventral spinal quadrant resulted in deterioration and instability of the locomotor rhythm. Injury to lateral or medial descending motor systems led to redistribution of the tone in antagonist muscles. Locomotion could be evoked by epidural stimulation within 20 h after complete transection of the spinal cord. The restoration of polysynaptic components in EMG responses correlated with recovery of the stepping function. The data obtained confirm that initiation of locomotion under epidural stimulation is caused by direct action on intraspinal systems responsible for locomotor regulation. With intact or partially injured spinal cord, this effect is under the influence of supraspinal motor systems correcting and stabilizing the evoked locomotor pattern.     

Spinal cord stimulation improves survival in ischemic skin flaps: an experimental study of the possible mediation by calcitonin gene-related peptide

Currently, spinal cord stimulation is used to treat ischemia and ischemic pain, with the best results observed in vasospastic cases. It was earlier demonstrated that spinal cord stimulation may attenuate experimentally induced vasospasm in an island flap in the rat. The present study was designed to investigate whether preemptive spinal cord stimulation could increase long-term flap survival and to explore the neurohumoral mediation of the effect. A total of 56 rats were implanted with chronic spinal cord stimulation systems. Three days later, a groin flap based on the superficial epigastric vessels was harvested, and the single feeding artery was occluded by a detachable microvascular clip. After 12 hours, the clip was removed. Flap survival was evaluated after 7 days. Immediately before flap surgery, two groups of animals received 30 minutes of stimulation using current clinical parameters and with stimulation amplitudes of 70 (n = 10) or 90 percent (n = 8) of that evoking muscular contractions. The outcomes in these groups were compared with those in two control groups (n = 20; n = 10). In one group, an additional calcitonin gene-receptor peptide (CGRP) antagonist was intravenously injected before stimulation (n = 8). In the control groups without stimulation, virtually all flaps necrotized. In treated groups, flap survival was 60 percent at the lower intensity and almost 90 percent at the higher one. The administration of a CGRP antagonist before treatment reduced its efficacy to below 40 percent survival. The differences between the untreated and treated groups were significant. The decrease in survival after CGRP-receptor block was significant in one of two tests. Preemptive spinal cord stimulation increases survival of skin flaps with critical ischemia. The effects are dependent on the stimulation intensity and are possibly mediated by the release of CGRP in the periphery.     

Effects of spinal cord stimulation on spasticity and spasms secondary to myelopathy

16 subjects with severe spasms secondary to traumatic and nontraumatic myelopathy underwent epidural spinal cord stimulation. 4 patients had a complete motor and sensory spinal cord lesion. 6 of the subjects with an incomplete spinal cord lesion were ambulatory. All patients had previously undergone extensive trials with medications and physical therapy. All 14 subjects in whom a satisfactory placement of the electrode could be obtained had a reduction in the severity of the spasms. In 6 patients, the spasms were almost abolished. Extremity, trunkal and abdominal spasms were affected. Clonus in the upper extremities was consistently reduced. Marked improvement in bladder and bowel function was observed in each of 2 subjects. In over 1-year follow-up, 5 subjects show persistence of the results, with less stimulation required to maintain the therapeutic effects. No neurological deterioration occurred following the procedure or after long-term spinal stimulation. 1 patient showed after several months of continuous stimulation increased voluntary motor control present only when spinal cord stimulation was activated. Complications included 1 system infection, 1 electrode migration, 1 wire breakage and skin breakdown at a connector site, development of high impedance in 1 electrode and 1 skin breakdown over the lead.     

Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli

The aim of the present study was to establish an experimental model, previously used in cat, for studying tachykinin release from the rat spinal cord in vivo and to compare the results with those obtained in vitro. Stimulation with pulses of 40 mM potassium or 10 microM capsaicin in the spinal cord superfusion fluid increased the release of substance P (SP)- and neurokinin A (NKA)-like immunoreactivity (LI) both in vivo and in vitro. The amounts of SP-LI and NKA-LI released by potassium in vitro were 1.02 +/- 0.12 and 1.17 +/- 0.22 fmol/mg tissue, respectively. Also the ratio between the amounts released by two consecutive potassium stimulations were similar for SP-LI and NKA-LI. Reversed-phase high performance liquid chromatography of the NKA-LI released in vitro by potassium or capsaicin revealed a major immunoreactive component coeluting with synthetic NKA. Despite the use of highly sensitive radioimmunoassays, basal release of SP-LI and NKA-LI was found only in 9 of 31 in vivo experiments. In these, peripheral electrical stimulation of the sciatic nerves (50 Hz, 50 V and 0.05 ms or 10 Hz, 10 V and 5 ms) induced an increase of the SP-LI and NKA-LI levels in the superfusates. This increase persisted for more than 40 min after a 2 min stimulation. In most experiments, however, no SP-LI or NKA-LI could be detected in the superfusates, neither at basal conditions nor following electrical nerve stimulation. Similarly, no release of SP-LI could be detected in response to various noxious mechanical, thermal or chemical stimuli applied to the skin. The present results demonstrate that the superfused rat spinal cord may be used to study in vivo release of tachykinins in response to intense chemical stimulation of the entire spinal cord. However, the method seems to be less suitable for studies of tachykinin release in response to electrical activation engaging only a few spinal segments or in response to natural noxious stimuli. The results obtained in vitro suggest that SP and NKA are released in equimolar amounts from the spinal cord upon stimulation with potassium.