Changes in extracellular potassium concentration in cat spinal cord in response to innocuous and noxious stimulation of legs with healthy and inflamed knee joints

Summary In 20 cats anaesthetized with alpha-chloralose and spinalized at the thoracolumbar junction we investigated the role of stimulation induced accumulation of extracellular potassium in the spinal cord in the processing of nociceptive discharges from the knee joint. For that we electrically stimulated the posterior articular nerve of the knee. We further performed innocuous and noxious stimulation of the knee and of other parts of the leg and studied the effect of an acute inflammation of the knee on [K⁺]₀ in the spinal cord. Innocuous stimulation of the skin (brushing or touching) and innocuous movements in the knee joint all induced rises in [K⁺]₀ which were maximal at recording depths of 1500 to 2200 m below the surface of the cord dorsum. Peak increases were 0.4 mM for touching the leg and 1.7 mM during rhythmic flexion/ extension of the knee joint. Noxious stimulation of the skin, the paw, the tendon and noxious movements of the knee joint also produced rises in [K⁺]₀, which were somewhat larger for the individual types of stimuli than those produced by innocuous intensities. Electrical stimulation of the posterior articular nerve induced rises in [K⁺]₀ by up to 0.6 mM. Stimulus intensities sufficient to activate unmyelinated group IV fibers were only slightly effective in raising [K⁺]₀ above the levels reached during stimulation of myelinated group II and III fibers. During development of an acute inflammation of the knee joint (induced by kaolin and carrageenan), increases in [K⁺]₀ and associated field potentials became larger by about 25%. We assume that this reflects an increase in neuronal responses. In conclusion, changes in [K⁺]₀ in the spinal cord are some-what larger during noxious stimulation than during innocuous stimulation. The absolute level reached depended more on the site and type of stimulation than on the actual stimulus intensity itself. Hence a critical role of spinal K⁺ accumulation for nociception is unlikely.     

Anaplastic Ependymoma of the Spinal Cord in Childhood A Case Report

We report a 6-year-old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cere-brospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed.     

Information Capacity of the Corticospinal Tract Recordings as a Neural Interface

Recording the motor output of the central nervous system from the cervical spinal cord was investigated as a method of generating voluntary command signals, potentially to be used in quadriplegic individuals. Corticospinal volleys evoked by motor cortex stimulation were recorded from the spinal cord surface with multicontact electrodes in anesthetized cats. The multicontact recordings were analyzed for their information-carrying capacity as a neural interface. Neural signals resulting from the stimulation of various points in the motor cortex were considered as symbols of an alphabet that were sent through a discrete information channel. The information capacity of this channel at the thermal noise level of the electrode contacts was calculated. The maximum information rate was 1.57 bits in a trial for a 4-symbol alphabet. The background noise that reduces the information rate to 50% of its maximum theoretical value was defined as the half-bitrate-noise-tolerance (HBR-NoiseTol) and used as a measure of symbol distinguishability. The HBR-NoiseTol for all trials on average was 24 +/- 12%, 18 +/- 10%, and 15 +/- 9% for interfaces with 2-, 3-, and 4-symbol alphabets (n = 11 trials). The average peak-to-peak amplitude of the neural volleys was 13.5 +/- 6.7 microV (n = 11). These results suggest that the corticospinal signals can be recorded with spatial selectivity from the spinal cord surface and thus warrant further investigation of their potential use for a spinal cord-computer interface.     

坐骨神经损伤后大鼠脊髓腰段前角AChE的变化

结扎切断 SD 大鼠左侧坐骨神经或前后根后,在一定的存活时间序列里,用 Olympus显徽镜的测光装置对经 EL—Badawi 氏改良法显色处理后的脊髓腰段前角乙酰胆硷酯酶(ACHE)进行了相对变化率(Xo/Xc—1)×100%的测定。结果发现坐骨神经切断术后,术侧脊髓前角 AChE10天后增高22.1%;术后25天时减少到-20.2%;60天时又再次增高22.8%,呈双峰夹低谷的变化曲线。切断前后根后,术侧脊髓前角 AChE10天后明显下降(-21.1%);提示外周神经受损部位不同,脊髓前角 AChE 发生变化的情况不同.根据分析,本文将双峰夹低谷曲线分为1.应激期;2.调整期;3.恢复期.外周神经受损后有关神经元将出现变性和再生现象.神经变性和再生过程中形态学方面的研究至今已有百余年的历史;神经递质及其代谢酶在神经系统中正常分布的研究也有了几十的年历史;但在神经变性和再生的过程中,神经递质及其代谢酶的动态变化的研究正在兴起。神经元受损后神经递质及其代谢酶的动态性变化,在一定程度上反映了神经细胞对伤害性刺激的反应。1987年 Malatova 在狗发现 AChE 在远侧残根中是先显著下降,后轻微下降;在近侧残根中和在前角中是先升后降.但在更长时间里的变化情况怎样?以及在大鼠脊髓前角中的变化情况又如何?这种变化与外周神经损伤部位的关系又怎样?目前尚无报导。为了探讨这些问题,本文应用组化方法进行染色,利用照相显微镜的曝光时间对AChE 的染色强度作了相对量的测定。     

Hormone-active intradural spinal metastasis of a prolactinoma — A case report

Summary A 44-year-old woman developed acute severe visual field defects and was operated on a macroprolactinoma. Since complete resection of the tumor was not possible, radiotherapy was performed and in addition to hormone replacement therapy, bromocriptine (up to 60 mg daily) was started without however complete normalization of PRL levels. Four years later PRL levels increased to 10⁵ µU/ml despite continuation of dopamin agonist (mesulergin) treatment. As shown by ophthalmological examination and computer tomography there were no signs of regrowth of the pituitary tumor. At that time the patient complained of severe lumbar pain and myelography revealed a tumor mass in the spinal cord (L₁–L₂). Since the spinal tumor was not removable, laminectomy was performed. Histology and immunohistochemistry demonstrated a metastasis of the prolactinoma. Radiotherapy and bromocriptine in extreme doses (140 mg daily) together with an antiestrogen were not able to improve the neurological deficits (paraparesis) and to lower the PRL levels. This case of a metastasis of a prolactinoma after operation, radiotherapy, and dopamin agonist treatment stresses the importance of close surveillance of patients with prolactinomas without PRL normalization during dopamin agonist therapy and shows for the first time the possibility of ectopic PRL production due to an intradural spinal metastasis.Abbreviations ACTH adrenocorticotropin - FSH folliclestimulating hormone - GH growth hormone - Gy Gray - L lumbar - LH luteinizing hormone - µU/ml microunits per milliliter - mU/ml milliunits per milliliter - PRL prolactin - TBG thyroxine-binding globulin - TSH thyrotropin - T₄ thyroxine - T₃ triiodothyronine     

Excitability of the soleus H-reflex arc during walking and stepping in man

Summary In eight normal subjects, the excitability of the soleus (Sol) H-reflex was tested in parallel with Sol length changes, EMGs of leg and thigh muscles and ground contact phases, during three different pacing movements: bipedal treadmill walking, single limb treadmill walking, and single-limb stepping on one spot. A computerized procedure was used which compensated for changes in stimulus effectiveness that occurred during free motion. In the three paradigms examined, significant excitability modulations were observed with respect to a control level determined in standing weight-bearing position. During bipedal treadmill walking, excitability was decreased in the early stance, maximally enhanced in the second half of the stance, and again decreased during the end-stance and the whole swing phase, with a minimum value around the toe off period. The main modulation pattern was retained during single-limb treadmill walking. During single-limb stepping on one spot, the stance-phase increase in excitability and the swing phase depression were still present. However, in the second half of the swing phase, reflex responsiveness returned to reference level, which was maintained during the subsequent contact period. Moreover, a decrease in reflex excitability was detected around the mid-stance. The time course of the described modulations was only partly correlated with the EMG and length changes of the Sol muscle. Furthermore, in the three movements tested, during the early stance phase, the excitability of the H-reflex arc did not correspond to the one expected on the basis of the available H-reflex studies performed under static conditions. It is suggested that, at least in certain stride phases (e.g. around the early contact period), an active regulation affects the transmission in the Sol myotatic arc during the pacing movements investigated.     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Synaptic connections from large afferents of wrist flexor and extensor muscles to synergistic motoneurones in man

 Short-latency excitatory Ia reflex connections were determined between pairs of human wrist flexor and extensor muscles. Spindle Ia afferents were stimulated by either tendon tap or electrical stimulation. The activity of voluntarily activated single motor units was recorded intramuscularly from pairs of wrist flexor or extensor muscles. Cross-correlation between stimuli and the discharge of the motor units provided a measure of the homonymous or heteronymous excitatory input to a motoneurone. Homonymous motoneurone facilitation was generally stronger than that of the heteronymous motoneurones. The principal wrist flexors, flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU), were tightly connected through a bidirectional short-latency reflex pathway. In contrast, the extensor carpi ulnaris (ECU) and the extensor carpi radialis (ECR) did not have similar connections. ECU motoneurones received no short-latency excitatory Ia input from the ECR. ECR motoneurones did receive excitatory Ia input from ECU Ia afferents; however, its latency was delayed by several milliseconds compared with other heteronymous Ia excitatory effects observed. The wrist and finger extensors were linked through heteronymous Ia excitatory reflexes. The reflex connections observed in humans are largely similar to those observed in the cat, with the exception of heteronymous effects from the ECU to the ECR and from the extensor digitorum communis (EDC) to the ECU, which are present only in humans. The differences in the reflex organization of the wrist flexors versus the extensors probably reflects the importance of grasping. Received: 19 August 1996 / Accepted: 6 March 1997     

Retention of a backward classically conditioned reflex response in spinal cat

Summary Retention of a backward classically conitioned reflex response was investigated in the spinal cat preparation. Facilitation of the flexion reflex was induced by the pairing of superficial peroneal nerve stimulation (30 Hz, 0.5 s), the US (unconditioned stimulus), with saphenous nerve stimulation (10 Hz, 1.5 s), the CS (conditioned stimulus). Both the US and CS were supramaximal for activation of A cutaneous afferent fibers. Experimental animals received 30 paired trials (US preceded CS by 0.25 s) with an intertrial interval (ITI) of three min. Control animals received the same stimuli but in an explicitly unpaired manner. Following acquisition, all animals received 30 additional CS-alone trials at five min intervals. This paradigm, which incorporated ITIs longer than those which had been used previously in backward conditioning studies, induced a long-lasting potentiation of the flexion reflex which appeared to be specific to spinal reflex pathways activated by A cutaneous fibers. The relevancy of these results to a more specific understanding of backward and forward classical conditioning in the spinal cat is discussed.Supported by NSF grants 8415917 and 8808495     

Extracellular ionic and volume changes: The role in glia—Neuron interaction

Activity-related changes in extracellular K⁺ concentration ([K⁺]_e), pH (pH_e) and extracellular volume were studied by means ofion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3–14 days of age (P3–P14). Concomitantly with the ionic changes, the extracellular space (ECS) volume fraction (α), ECS tortuosity (λ) and non-specific uptake (k′), three parameters affecting the diffusion of substances in nervous tissue, were studied in the rat spinal cord gray matter. In adult rats, repetitive electrical nerve stimulation (10–100 Hz) elicited increases in [K⁺]_e of about 2.0–3.5 mm, followed by a post-stimulation K⁺-undershoot and triphasic alkaline-acid-alkaline changes in pH_e with a dominating acid shift. The ECS volume in the adult rat occupies about 20% of the tissue, α = 0.20 ± 0.003, λ = 1.62 ± 0.02 and k′ = 4.6 ± 0.4 × 10⁻³s⁻¹ (n = 39). In contrast, in pups at P3–P6, the [K⁺]_e increased by as much as 6.5 mm at a stimulation frequency of 10 Hz, i.e. K⁺ ceiling level was elevated, and there was a dominating alkaline shift. An increase in [K⁺]_e as large as 1.3–2.5 mm accompanied by an alkaline shift was evoked by a single electrical stimulus. The K⁺ ceiling level and alkaline shifts decreased with age, while an acid shift, which was preceded by a small initial alkaline shift, appeared in the second postnatal week. In pups at P1–P2, the spinal cord was X-irradiated to block gliogenesis. The typical decrease in [K⁺]_e ceiling level and the development of the acid shift in pH_e at P10–P14 were blocked by X-irradiation. Concomitantly, continuous development of glial fibrillary acidic protein positive reaction was disrupted and densely stained astrocytes in gray matter at P10–P14 revealed astrogliosis.The alkaline, but not the acid, shift was blocked by Mg²⁺ and picrotoxin (10⁻⁶m). Acetazolamide enhanced the alkaline but blocked the acid shift. Furthermore, the acid shift was blocked, and the alkaline shift enhanced, by Ba²⁺, amiloride and SITS. Application of glutamate or gamma-aminobutyric acid evoked an alkaline shift in the pH_e baseline at P3–P14 as well as after X-irradiation. The results suggest that the activity-related acid shifts in pH_e are related to membrane transport processes in mature glia, while the alkaline shifts have a postsynaptic origin and are due to activation of ligand-gated ion channels.At P4–P6, the ECS volume was almost double that in adult rats, α = 0.37 ± 0.01 (n = 17), the ECS tortuosity was significantly higher, λ = 1.78 ± 0.02, while the non-specific uptake was not significantly different, k′ = 3.61 ± 0.56 × 10⁻³ s⁻¹. The α gradually decreased to about 24% at P12. In adult rats, electrical or adequate stimulation evoked a shrinkage of the extracellular space by 20–50%, while no significant changes in ECS volume were found in P3–P6. We conclude that the [K⁺]_e ceiling level, character of the pH_e transients, the size of the ECS volume and the activity-related ECS shrinkage are closely related to gliogenesis.