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Background "Diffuse midline glioma, H3 K27M-mutant" (DMG) mainly arises within the pontine, thalamic, and spinal cord regions. Because of the rarity of spinal cord gliomas, the general knowledge surrounding DMGs is mainly based on pontine and thalamic gliomas, whereas tumor location tends to influence the clinicopathological features and prognosis. Objective To determine the clinicopathological characteristics and molecular profiles of DMGs located in the spinal cord. Methods The clinical and molecular pathologic features and prognosis were comprehensively analyzed in a series of 44 patients with spinal cord DMGs. Results The median age was 36 yr, and 88.7% of patients (39/44) were adults (≥18 yr). Histopathologically, malignant grades included grade II (16 cases), grade III (20 cases), and grade IV (8 cases). Compared with patients with histological grade IV, patients with lower histological grade (grade II/III) were older (37 vs 24 yr, P = .020) and were associated with longer overall survival (24.1 vs 8.6 mo, P = .007). All 30 tested tumors were isocitrate dehydrogenase (IDH) wild type, and 96% of cases (22/23) presented with unmethylated O6-methylguanine-DNA methyltransferase. Univariate and multivariate analyses showed that histological grade and presurgery McCormick Scale scores were independent prognostic factors for overall survival, whereas extensive surgical resection and chemoradiotherapy were not significantly associated with improved survival. The most frequent anatomic locations were the cervical enlargement (C4-T1, n = 16) and conus medullaris (T12-L1, n = 13), which exhibited distinctive clinical characteristics and molecular features. Conclusion The findings provide guidelines for the evidence-based practice of the specialized management of spinal cord DMGs.

Following a program of resistance training, there are neural and muscular contributions to the gain in strength. Here, we measured changes in important central motor pathways during strength training in 2 female macaque monkeys. Animals were trained to pull a handle with one arm; weights could be added to increase load. On each day, motor-evoked potentials in upper limb muscles were first measured after stimulation of the primary motor cortex (M1), corticospinal tract (CST), and reticulospinal tract (RST). Monkeys then completed 50 trials with weights progressively increased over 8-9 weeks (final weight ∼6 kg, close to the animal's body weight). Muscle responses to M1 and RST stimulation increased during strength training; there were no increases in CST responses. Changes persisted during a 2 week washout period without weights. After a further 3 months of strength training, an experiment under anesthesia mapped potential responses to CST and RST stimulation in the cervical enlargement of the spinal cord. We distinguished the early axonal volley and later spinal synaptic field potentials, and used the slope of the relationship between these at different stimulus intensities as a measure of spinal input-output gain. Spinal gain was increased on the trained compared with the untrained side of the cord within the intermediate zone and motor nuclei for RST, but not CST, stimulation. We conclude that neural adaptations to strength training involve adaptations in the RST, as well as intracortical circuits within M1. By contrast, there appears to be little contribution from the CST. SIGNIFICANCE STATEMENT We provide the first report of a strength training intervention in nonhuman primates. Our results indicate that strength training is associated with neural adaptations in intracortical and reticulospinal circuits, whereas corticospinal and motoneuronal adaptations are not dominant factors.

Coupling between cervical and lumbar spinal networks (cervico-lumbar coupling) is vital during human locomotion. Impaired cervico-lumbar coupling after neural injuries or diseases can be reengaged via simultaneous arm and leg cycling training. Sensorimotor circuitry including cervico-lumbar coupling may further be enhanced by non-invasive modulation of spinal circuity using transcutaneous spinal cord stimulation (tSCS). This project aimed to determine the effect of cervical, lumbar, or combined tSCS on spinal reflex (Hoffmann [H-]) and corticospinal (motor evoked potential [MEP]) excitability during a static or cycling cervico-lumbar coupling task. Fourteen neurologically intact study participants were seated in a recumbent leg cycling system. H-reflex and MEP amplitudes were assessed in the left flexor carpi radialis (FCR) muscle during two tasks (Static and Cycling) and four conditions: (1) No tSCS, (2) tSCS applied to the cervical enlargement (Cervical); (3) tSCS applied to the lumbar enlargement (Lumbar); (4) simultaneous cervical and lumbar tSCS (Combined). While cervical tSCS did not alter FCR H-reflex amplitude relative to No tSCS, lumbar tSCS significantly facilitated H-reflex amplitude by 11.1%, and combined cervical and lumbar tSCS significantly enhanced the facilitation to 19.6%. Neither cervical nor lumbar tSCS altered MEP amplitude alone (+4.9 and 1.8% relative to legs static, No tSCS); however, combined tSCS significantly increased MEP amplitude by 19.7% compared to No tSCS. Leg cycling alone significantly suppressed the FCR H-reflex relative to static, No tSCS by 13.6%, while facilitating MEP amplitude by 18.6%. When combined with leg cycling, tSCS was unable to alter excitability for any condition. This indicates that in neurologically intact individuals where interlimb coordination and corticospinal tract are intact, the effect of leg cycling on cervico-lumbar coupling and corticospinal drive was not impacted significantly with the tSCS intensity used. This study demonstrates, for the first time, that tonic activation of spinal cord networks through multiple sites of tSCS provides a facilitation of both spinal reflex and corticospinal pathways. It remains vital to determine if combined tSCS can influence interlimb coupling after neural injury or disease when cervico-lumbar connectivity is impaired.

Renshaw cells mediate recurrent inhibition between motoneurons within the spinal cord. The function of this circuit is not clear; we previously suggested based on computational modeling that it may cancel oscillations in muscle activity around 10 Hz, thereby reducing physiological tremor. Such tremor is especially problematic for dexterous hand movements, yet knowledge of recurrent inhibitory function is sparse for the control of the primate upper limb, where no direct measurements have been made to date. In this study, we made intracellular penetrations into 89 motoneurons in the cervical enlargement of four terminally anesthetized female macaque monkeys, and recorded recurrent IPSPs in response to antidromic stimulation of motor axons. Recurrent inhibition was strongest to motoneurons innervating shoulder muscles and elbow extensors, weak to wrist and digit extensors, and almost absent to the intrinsic muscles of the hand. Recurrent inhibitory connections often spanned joints, for example from motoneurons innervating wrist and digit muscles to those controlling the shoulder and elbow. Wrist and digit flexor motoneurons sometimes inhibited the corresponding extensors, and vice versa. This complex connectivity presumably reflects the flexible usage of the primate upper limb. Using trains of stimuli to motor nerves timed as a Poisson process and coherence analysis, we also examined the temporal properties of recurrent inhibition. The recurrent feedback loop effectively carried frequencies up to 100 Hz, with a coherence peak around 20 Hz. The coherence phase validated predictions from our previous computational model, supporting the idea that recurrent inhibition may function to reduce tremor.SIGNIFICANCE STATEMENTWe present the first direct measurements of recurrent inhibition in primate upper limb motoneurons, revealing that it is more flexibly organized than previous observations in cat. Recurrent inhibitory connections were relatively common between motoneurons controlling muscles that act at different joints, and between flexors and extensors. As in the cat, connections were minimal for motoneurons innervating the most distal intrinsic hand muscles. Empirical data are consistent with previous modeling: temporal properties of the recurrent inhibitory feedback loop are compatible with a role in reducing physiological tremor by suppressing oscillations around 10 Hz.

The aim of this study was to estimate and compare volume fraction values of grey matter (substantia grisea) in thecervical enlargement (intumescentia cervicalis) using stereological methods for two different types of birds. Ten pairs of quails andchickens were included in this study as one of them is flying and the other one is flightless bird species. The tissues cut into serialsections of 5 µm thickness were selected according to systematic random sampling and stained with cresyl violet. Volume and volumefractions were calculated in accordance with the Cavalieri principle. Student’s t-test was used to evaluate volume fraction differencesamong the species. The volume fractions of grey matter in cervical enlargement of chicken and quail were 0.277 ± 0.005 and 0.346 ±0.014 (Mean ± Standart Deviation), respectively (p < 0.001). There was a significant difference between chicken and quail cervicalenlargements in terms of volume fraction values of grey matter. On the other hand, the Cavalieri principle was considered as anunbiased, accurate and effective method for volume and volume fraction estimations.&nbsp

In the present study, volume values of the cervical segments in the spinal cords of adult ducks weighing 3-4 kg were investigated. Volume values of the grey matter and white matter in the cervical segment of the spinal cord of the ducks were examined stereologically. Ten ducks (genus Anas) without regarding the sex of the animals. All animals were perfused using 10% formaldehyde. The animals were kept in 10% formaldehyde for 1 week to ensure fixation. The ducks were then dissected. The cervical segments were uncovered by removing the cervical vertebrae. Tissue samples were obtained from each of the cervical spinal segments, and 5-μm-thick cross-sections were obtained from these samples. Sampling was performed at a ratio of 1/250 to obtain 12 cross-sections from each cervical segment of the animals. These sections were stained using the hematoxylin and eosin staining technique. Photos were taken under a microscope. Volume values of whole tissue, grey matter, and white matter were calculated for each cervical segment of the spinal cord of the ducks. Cavalieri's principle was employed for the calculation. As a result, the vertebral column was used as a guide to identify the cervical segments of the spinal cord. The cervical segments were also obtained by dissection without using a decalcification process. It was determined that the number of segments was 15. When mean volume values of the whole cervical segment of the spinal cord in the ducks were evaluated, the highest mean volume was determined as 4.224 mm 3 " role="presentation"> 3 3 ^{3} in segment C15. The cervical spinal segment with the lowest value of white matter was C7 (0.915 mm 3 " role="presentation"> 3 3 ^{3} ). When the volume values of the grey matter of the cervical segments of the ducks were examined, it was determined that segments C14 and C15 had the highest values, calculated as 0.511 mm 3 " role="presentation"> 3 3 ^{3} and 0.513 mm 3 " role="presentation"> 3 3 ^{3} , respectively. It was determined that segments C12, C13, C14, and C15 were involved in the cervical enlargement.

Objective. Spinal stimulation is a promising method for restoring the function of paralyzed limbs following neurological damage to descending pathways. The present study examined the forelimb movements and muscle responses evoked by subdural spinal stimulation of the cervical cord in sedated monkeys or during an arm-reaching task. Approach. We chronically implanted a platinum subdural electrode array with eight channels over the dorsal-lateral aspect of the cervical enlargement. The electrodes had a diameter of 1 mm and an inter-electrode center-to-center distance of 3 mm. Subdural spinal micro-stimulation was delivered at sites while the monkeys were sedated or performed arm-reaching movements. Main results. The evoked movements clearly showed the somatotopic map of the output sites; the electrodes located on the rostral cervical cord tended to induce movements of the proximal arm, whereas the caudal electrodes tended to induce movements of the distal joints, such as the wrist and digits. To document the muscle responses evoked by subdural spinal stimulation, stimulus-triggered averages of rectified electromyograms were compiled when the monkeys performed an arm-reaching task or were sedated. Under sedation, evoked facilitative muscle responses were observed in vicinity muscles. In contrast, during the task, stimulation evoked facilitative or suppressive responses in multiple muscles, including those located on proximal and distal joints, while somatotopy became blurred under sedation. Furthermore, stimulation during tasks activated synergistic muscle groups. For example, stimuli strongly facilitated finger extensor muscles, but suppressed the antagonist muscles. Significance. These dynamic changes in muscle representation by subdural cervical spinal stimulation between sedated and awake states help our understanding of the nature of spinal circuits and will facilitate the development of neuroprosthetic technology to regain motor function after neural damage to the descending pathways.

Background: Diabetic neuropathy is a common chronic complication in diabetes mellitus. Such neuropathy associates with chronic inflammation and immune system activation. Microglia, a type of neuroglia, are involved in the immune system and are found in grey and white matter of the central nervous system, such as the brain and spinal cord. The spinal cord connects the peripheral nervous system and the higher brain centre. Hyperglycaemia during diabetes mellitus has been found to activate and increase number of microglia in the dorsal grey horn or column of the lumbar segments in spinal cord, which release several cytokines in the development of hypersensitivity in diabetic neuropathic pain. Materials and methods: Therefore, in this study, anatomical alterations of rat spinal microglia in all areas (dorsal, intermediate and ventral columns of grey matter and dorsal, lateral and ventral funiculi of white matter) in cervical enlargement, thoracic level and lumbosacral enlargement were observed in early stage of diabetic conditions by using light and transmission electron microscopies. Results: The numbers of microglia in all parts of grey and white matter of all spinal levels significantly increased in the diabetic group. The structures and ultrastructures of microglia in grey and white matter at cervical enlargement, thoracic level and lumbosacral enlargement similarly changed in diabetes. In diabetic rats, microglia became hypertrophied with a pale nucleus. Moreover, short fragments of rough endoplasmic reticulum, elevated numbers of lysosomes and numerous actin filaments in the cytoplasm were examined. Microglial phagocytosis of myelin and axonal debris were also observed. In this investigation, the morphology of spinal microglia during short-term diabetes became activated during hyperglycaemia. Conclusions: It is suggested that these changes may be involved in the development of diabetic neuropathic pain in the spinal cord.

NT is a 15-year-old post-menarchal girl; she was complaining of cervical enlargement, a weight loss of 21 kg in 3 months, night sweats, and fever. Clinical examination of the patient found a 2 cm fixed painless and firm right lateral jugular lymphadenopathy. The left cervical lymphadenopathy biopsy revealed a scleronodular Hodgkin’s disease. The patient’s disease was staged IIBb with mediastinal bulky according to the Ann Arbor classification system.

Introduction: To illuminate the mechanism of neuromuscular junction involvement by analyzing the features of a slow-rate repetitive nerve simulation (RNS) and EMG in amyotrophic lateral sclerosis (ALS) patients. Methods: We retrospectively analyzed relationship between clinical features and the decremental response in RNS in 184 sporadic ALS patients. Results: (1) 44.3 and 43.5% of compound muscle action potentials (CMAP) decrement were more than –10% in deltoid muscle (Del) and Trap; (2) ALS patients were divided into RNS positive (RNS+) and RNS negative (RNS–) group according to decremental percentage of RNS greater or less than –10%. The diagnostic delay time was shorter and ALSFRS-r score was lower in RNS+ than RNS– group (p < 0.05), progression rate had no difference. The incidence of RNS+ decrement was higher in cervical enlargement onset and definite diagnostic degrees (p < 0.05); (3) In EMG+ group, the CMAP amplitude was lower (Axillary: 3.1 ± 1.91 vs. 5.92 ± 2.896, p = 0.000; Accessory: 2.68 ± 1.349 vs. 3.65 ± 1.53, p = 0.002), decremental percentage of RNS was higher (Axillary: –10.85 ± 7.508 vs. –5.43 ± 8.425, p = 0.000; Accessory: –13.11 ± 7.539 vs. –8.03 ± 5.999, p = 0.000) compared with needle EMG– group whether in Del or Trap; (4) Decremental response of RNS was positively correlated with the CMAP amplitude in Axillary and Accessory nerves (R = 0.201, p < 0.0001; R = 0.103, p < 0.0001). Conclusions: Our clinical results support the mechanism of decremental phenomenon of RNS is immature sprouts and unstable conduction by the degenerating axons in ALS patients. The more serious the axon damage, the more significant the RNS decremental response. But decremental response dose not effect disease progression.

A chronic complication of diabetes mellitus (DM), diabetic neuropathy, causes neurodegeneration leading to the development of neuropathic pain and sensation loss, particularly in the hands and arms. The cervical enlargement of the spinal cord sends the nerve supply to the hands and arms. Moreover, astrocytes effectively provide structural and functional maintenance of neurons in the spinal cord. Nevertheless, there is very little research concerning the ultrastructural changes of diabetic spinal astrocytes in the cervical enlargement. Thus, in this study, the ultrastructural changes of protoplasmic and fibrous astrocytes in streptozotocin (STZ)-induced diabetic and control rats using transmission electron microscopy (TEM) were examined and compared. Thirteen male diabetic and six male control rats were intraperitoneally administered with either STZ in citrate buffer or only the buffer solution, respectively. Rats were sacrificed at four (short term) and twenty-four weeks (long term) after induction of DM. Then, the cervical enlargements were collected for TEM processing. Under TEM, the morphologies of protoplasmic and fibrous astrocytes were similarly changed in each group. In the short-term DM model animals, hypertrophic nuclei with heterochromatin clumping were seen in both types of astrocytes. The rough endoplasmic reticulum (rER), Golgi complexes, and mitochondria were distended. Moreover, augmented glial fibrils were seen in astrocytic processes. In the long-term diabetes, increased heterochromatin clumping with severely disrupted nuclear membranes was seen in both types of astrocytes. The rER, Golgi complexes, and mitochondria were extremely degenerated. Disruptions of astrocytic processes were also observed. These results indicate that DM leads to abnormalities of both protoplasmic and fibrous astrocytes, which are possibly involved in the impairment of neuronal function that causes diabetic neuropathy. Thus, this basic knowledge can support better understanding of the pathogenesis in diabetic neuropathy. Key words: Astrocytes, cervical enlargement, spinal cord, diabetes mellitus, streptozotocin.

Objectives To develop the first high-resolution, multi-scale model of cervical non-invasive vagus nerve stimulation (nVNS) and to predict vagus fiber type activation, given clinically relevant rheobase thresholds. Methods An MRI-derived Finite Element Method (FEM) model was developed to accurately simulate key macroscopic (e.g., skin, soft tissue, muscle) and mesoscopic (cervical enlargement, vertebral arch and foramen, cerebral spinal fluid [CSF], nerve sheath) tissue components to predict extracellular potential, electric field (E-Field), and activating function along the vagus nerve. Microscopic scale biophysical models of axons were developed to compare axons of varying size (Aα-, Aβ- and Aδ-, B-, and C-fibers). Rheobase threshold estimates were based on a step function waveform. Results Macro-scale accuracy was found to determine E-Field magnitudes around the vagus nerve, while meso-scale precision determined E-field changes (activating function). Mesoscopic anatomical details that capture vagus nerve passage through a changing tissue environment (e.g., bone to soft tissue) profoundly enhanced predicted axon sensitivity while encapsulation in homogenous tissue (e.g., nerve sheath) dulled axon sensitivity to nVNS. Conclusions These findings indicate that realistic and precise modeling at both macroscopic and mesoscopic scales are needed for quantitative predictions of vagus nerve activation. Based on this approach, we predict conventional cervical nVNS protocols can activate A- and B- but not C-fibers. Our state-of-the-art implementation across scales is equally valuable for models of spinal cord stimulation, cortex/deep brain stimulation, and other peripheral/cranial nerve models.

The majority of spinal cord injuries (SCI) occur at the cervical level, which results in significant impairment. Neurologic level and severity of injury are primary endpoints in clinical trials; however, how level-specific damages relate to behavioural performance in cervical injury is incompletely understood. We hypothesized that ascending level of injury leads to worsening forelimb performance, and correlates with loss of neural tissue and muscle-specific neuron pools. A direct comparison of multiple models was made with injury realized at the C5, C6, C7 and T7 vertebral levels using clip compression with sham-operated controls. Animals were assessed for 10 weeks post-injury with numerous (40) outcome measures, including: classic behavioural tests, CatWalk, non-invasive MRI, electrophysiology, histologic lesion morphometry, neuron counts, and motor compartment quantification, and multivariate statistics on the total dataset. Histologic staining and T1-weighted MR imaging revealed similar structural changes and distinct tissue loss with cystic cavitation across all injuries. Forelimb tests, including grip strength, F-WARP motor scale, Inclined Plane, and forelimb ladder walk, exhibited stratification between all groups and marked impairment with C5 and C6 injuries. Classic hindlimb tests including BBB, hindlimb ladder walk, bladder recovery, and mortality were not different between cervical and thoracic injuries. CatWalk multivariate gait analysis showed reciprocal and progressive changes forelimb and hindlimb function with ascending level of injury. Electrophysiology revealed poor forelimb axonal conduction in cervical C5 and C6 groups alone. The cervical enlargement (C5-T2) showed progressive ventral horn atrophy and loss of specific motor neuron populations with ascending injury. Multivariate statistics revealed a robust dataset, rank-order contribution of outcomes, and allowed prediction of injury level with single-level discrimination using forelimb performance and neuron counts. Level-dependent models were generated using clip-compression SCI, with marked and reliable differences in forelimb performance and specific neuron pool loss.

A rare case of mixed carcinoma of the cervix is reported, composed of a small and large cell neuroendocrine carcinoma. Neuroendocrine cervical carcinomas are very rare and aggressive. The prognosis is very poor despite multimodal treatment. Earlier reports have shown that the majority of patients present with advanced stage disease, have lymph node metastasis, and are at a high risk for recurrence and disease progression. In this study, we report the case of a 26-year-old woman with composite small and large cell neuroendocrine carcinoma of the cervix. A woman presented with vaginal bleed since 2 months of presentation. Gynecologic examination revealed cervical enlargement, and punch biopsy of the cervical lesion was performed. The biopsy was disclosed a large cell neuroendocrine carcinoma. The patient underwent a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The final histopathologic findings are mixed small and large cell neuroendocrine carcinoma of cervix.

To characterize waveform changes of descending spinal cord evoked potentials (D-SCEPs) seen in cervical spondylotic myelopathy (CSM).Intraoperative D-SCEP recording from serial intervertebral discs after transcranial electrical stimulation in 19 CSM patients with cord compression at a single level.Compared to the baseline (100%) obtained one level rostrally, the D-SCEP recorded at the compression site showed a significantly (p0.001) decreased amplitude (48%) and area (48%) of negative peak and increased amplitude (171%) and area (279%) of initial-positive peak. The degree in reduction of negative peak remained the same irrespective of the cord level involved, whereas enhancement of the positive peak tended to diminish with a more caudal compression.In intraoperative electrophysiological studies of CSM with D-SCEP, an abrupt reduction of the negative peak accompanied by an enhancement of the initial-positive peak helps identify the site of conduction block. We speculate that progressive loss of the descending motor volleys at the synapses in the cervical enlargement may account for limited or absent enhancement of positive peak seen caudally.The current finding helps us understand the pros and cons of various electrophysiologic techniques for intraoperative localization of maximal cord involvement in CSM.

To further our understanding of the corticospinal projection (CSP) from the hand/arm representation of the primary motor cortex (M1), high-resolution anterograde tracing methodology and stereology were used to investigate the terminal distribution of this connection at spinal levels C5 to T1. The highest number of labeled terminal boutons occurred contralaterally (98%) with few ipsilaterally (2%). Contralaterally, labeled boutons were located within laminae I–X, with the densest distribution found in lamina VII and, to a lesser extent, laminae IX and VI. Fewer terminals were found in other contralateral laminae. Within lamina VII, terminal boutons were most prominent in the dorsomedial, dorsolateral, and ventrolateral subsectors. Within lamina IX, the heaviest terminal labeling was distributed dorsally. Ipsilaterally, boutons were found in laminae V–X. The most pronounced distribution occurred in the dorsomedial and ventromedial sectors of lamina VII and fewer labeled boutons were located in other ipsilateral laminae. Segmentally, contralateral lamina VII labeling was highest at levels C5–C7. In contrast, lamina IX labeling was highest at C7–T1 and more widely dispersed among the quadrants at C8–T1. Our findings suggest dominant contralateral influence of the M1 hand/arm CSP, a contralateral innervation pattern in lamina VII supporting Kuypers (1982) conceptual framework of a “lateral motor system,” and a projection to lamina IX indicating significant influence on motoneurons innervating flexors acting on the shoulder and elbow rostrally (C5–C7), along with flexors, extensors, abductors and adductors acting on the digits, hand and wrist caudally (C8–T1). J. Comp. Neurol. 521:4205–4235, 2013. © 2013 Wiley Periodicals, Inc.

Propriospinal pathways, consisting of axons from interneurons that project to other spinal segments, have been implicated as likely candidates to mediate interlimb coordination in developing and adult mammals during quadrupedal locomotion. The superficial thoracic ventrolateral funiculus (VLF) contains both ascending and descending axons, and when stimulated can induce alternating rhythmic locomotor-like activity in the lumbar ventral roots of the isolated neonatal rat spinal cord. The goal of this work was to characterize the synaptic inputs onto cervical neurons from ascending axons in the VLF. Sprague-Dawley rats (P4-P7) were deeply anesthesized with halothane and their spinal cords were isolated, removed, and maintained in vitro. Intracellular recordings were made from 68 cervical (C5-C7) neurons having 71 latency classifications in response to thoracic VLF stimulation. Antidromic (n=35), monosynaptic (n=2), di-or tri-synaptic (n=18) and long-latency polysynaptic (n=16) responses were recorded. Recordings from reduced preparations (mid-sagittal section at C5-C7) suggest that much of the delay in the long-latency polysynaptic responses require a bilaterally intact cervical spinal cord. Fifty-three percent (17/32) of the VLF responsive cervical interneurons tested also exhibited long latency excitatory responses to lumbar dorsal root stimulation suggesting that many of the cervical VLF responsive interneurons receive indirect input from lumbar primary afferents. We hypothesize that the VLF contains a population of ascending axons originating from lumbar propriospinal interneurons that can influence cervical inter- and motoneurons. These ascending VLF axons may participate in interlimb coordination by providing moment-by-moment feedback to the cervical enlargement of lumbar central pattern generator and/or hindlimb proprioceptive activity.

The objective of this study was to analyze the influence of different methods of cervical prepare in determining the first file of the apical preparation of root canal and working length. Thirty mesiobuccal fully formed roots of upper first permanent molars humans were used and the root canals were initially cleaned with K-file #10. Then, the teeth were randomly divided into three groups according to the type of enlargement: group I: ProTaper S1, SX; group II: K3 Orifice Opener 25.10 and 25.08; and group III: technique with hybrid K-type hand files and gates glidden drills # 3 and # 2. The specimens were taken to a stereomicroscope to evaluate the adaptation of the first file in the dentinal walls at length established. The data were submitted to Kruskal-Wallis and Wilcoxon tests. The reliability of the apex locator methods was performed by Spearman test. All groups showed statistically significant difference in the length of root canals after preparation of the cervical third (p < 0.05). The level of agreement between the measurement and visual electronics was higher (r = 98.07%) before the cervical enlargement, compared to that reported after cervical preparation (r = 96.42%) (p < 0.0001). Based on the methodology, was possible to conclude that cervical and middle thirds prepare were important to determine the first file diameter and it did lead to a decrease in the working length. The electronic apex was effective to determine the working length. How to cite this article Pires LB, Bueno C, Albergaria S, Bandéca MC, Semenoff-Segundo A, Porto AN, Borges; H. Influence of the Cervical Enlargement in Determining the Diameter of the First File and Establishing the Working Length. World J Dent 2013;4(3):164-169.

Minimally invasive endodontics emphasizes preservation of a maximal amount of healthy tooth tissue. However, whether the tooth structure preserved by minimally invasive endodontics can maintain higher fracture resistance is unclear. This study aimed to compare the biomechanics on teeth after minimally invasive (MI) preparation and straight-line (SL) preparation using finite element analysis. Six finite element analysis models of a mandibular first molar were constructed and divided into two groups (MI and SL). Two loads of 250 N, one vertically stimulating the vertical masticatory force and the other given 45° to the longitudinal axis of the tooth, were applied. Stresses in the teeth were calculated and analyzed. Under both vertical and 45° loads, the greatest stresses were located at the margin of the cavities on the occlusal surfaces. The stress concentration areas of teeth with minimally invasive access cavities were smaller than those of teeth prepared with straight-line opening in coronal and cervical areas. The stress concentration points in the cervical areas increased with the increase of canal taper in the coronal third. Minimally invasive access preparation reduced the stress distribution in crown and cervical regions. A smaller taper cervical enlargement caused lower stress in the cervical region.

Proprioceptive afferent (PA) information is integrated with signals from descending pathways, including the corticospinal tract (CST), by spinal interneurons in the dorsal horn and intermediate zone for controlling movements. PA spinal projections, and the reflexes that they evoke, develop prenatally. The CST projects to the spinal cord postnatally, and its connections are subsequently refined. Consequently, the tract becomes effective in transmitting control signals from motor cortex to muscle. This suggests sequential development of PAs and the CST rather than co-development. In this study we determined if there was also late postnatal refinement of PA spinal connections, which would support PA-CST co-development. We examined changes in PA spinal connections at 4 weeks of age, when CST terminations are immature, at 8 weeks, after CST refinement, and at 11 weeks, when CST terminations are mature. We electrically stimulated PA afferents in the deep radial nerve. Evoked PA responses were small and not localized at 4 weeks. By 8 and 11 weeks, responses were substantially larger and maximal in laminae VI and dorsal VII. We used intramuscular injection of cholera toxin β subunit to determine the distribution of PAs from the extensor carpii radialis muscle in the cervical enlargement at the same ages as in the electrophysiological studies. We found a reduction of the distribution of PAs with age that paralleled the physiological changes. This age-related sharpening of PA spinal connections also paralleled CST development, suggesting coordinated PA-CST co-development rather than sequential development. This is likely to be important for the development of adaptive motor control.

The motor effects induced by pulsed magnetic fields (PMF) projected onto the lumbar and cervical spinal cord were studied in decerebrate cats. A magnetic coil (inductor) of diameter 8 cm was positioned 1–2 cm above the surface of the spinal cord. Stimulation of the spinal cord with PMF was performed in two regimes: with single impulses with an intensity of 0.5–1 T and with continuous rhythmic stimulation at a frequency of 1 Hz and an intensity of 0.5 T. Application of single stimuli to the lumbar enlargement evoked reflex responses in the proximal and distal hindlimb muscles. Rhythmic stimulation initiated locomotor activity of the limb on a running treadmill, i.e., activated the neural locomotor network of the spinal cord (stepping movement generator). Magnetic stimulation of the lumbar enlargement evoked coordinated stepping movements of the hindlimbs only. Application of PMF to the cervical enlargement induced coordinated stepping movements of all four limbs, hindlimb movements starting before forelimb movements. After cessation of magnetic stimulation, the limbs completed several further coordinated movement cycles. This is the first report of the triggering of limb stepping movement generators with PMF in decerebrate cats. The results obtained here demonstrate that the neural locomotor networks of the spinal cord can be activated noninvasively and open new perspectives for the clinical use of PMF.

We studied the number, location and size of long descending propriospinal tract neurons (LDPT), located in the cervical enlargement (C3-C6 spinal levels), and short thoracic propriospinal neurons (TPS), located in mid-thoracic spinal cord (T5-T7 spinal levels), 2, 6 and 16 weeks following a moderate low thoracic (T9) spinal cord contusion injury (SCI; 25 mm weight drop) and subsequent injections of fluorogold into the upper lumbosacral enlargement (L2-L4 spinal levels). Retrograde labeling showed that approximately 23% of LDPT and 10% of TPS neurons were labeled 2 weeks after SCI, relative to uninjured animals. No additional significant decrease in number of labeled LDPT and TPS cells was found at the later time points examined, indicating that the maximal loss of propriospinal neurons in these two subpopulations occurs within the first 2 weeks post-SCI. The distribution of labeled cells post-moderate SCI was similar to normal in terms of their location within the gray matter. However, there was a significant change in the size (cross sectional area) of labeled neurons following injury, relative to uninjured controls, indicating a loss in the number of the largest class of propriospinal neurons. Interestingly, the number of labeled LDPT and TPS neurons was not significantly different following different injury severities. Although the rostro-caudal extent of the lesion site expanded between 2 and 16 weeks following injury, there was no significant difference in the number of propriospinal neurons that could be retrogradely labeled at these time points. Possible reasons for these findings are discussed.

Lamina I of the rat spinal cord contains neurons that project to various brain areas including thalamus, periaqueductal grey matter (PAG), lateral parabrachial area (LPb), caudal ventrolateral medulla and a region in dorsal medulla that includes the nucleus tractus solitarius and dorsal reticular nucleus. We have shown that spinothalamic lamina I neurons are infrequent in rat lumbar enlargement, where they constitute approximately 5% of the estimated 400 projection neurons on each side of the L4 segment (Al-Khater and Todd, 2009). They are more numerous in cervical enlargement, but the total number of lamina I projection neurons in this region was not known. Here we have used paired injections of retrograde tracers into the brainstem to estimate the number of lamina I projection cells in the C7 segment. Our results suggest that there are approximately 215 lamina I projection cells per side, and that spinothalamic cells therefore make up approximately 42% of this population. The proportion of lamina I projection neurons labelled from PAG is higher in cervical than lumbar enlargement, while the proportion labelled from dorsal medulla is similar in the two regions. We also found that lamina I cells in L4 that project to the dorsal medulla are included in the population retrogradely labelled from LPb, thus confirming the estimate that there are around 400 lamina I projection cells in this segment.

Background Intrigued by the two postulations of Rene Bourdiol, the one on the influence of the helix border on the segmental innervation of the body and the other on the differentiation into an anterior sensory side and a posterior motor side, we looked for further clinical evidence. Aim The aim is to present the elaboration of a chart of the helix border with its segmental indications. Method In a series of two articles we present a clinical body of evidence for the elaboration of the segmental chart of the helix border. This evidence was found by detection of painful points in the ear of patients with different diagnoses. Results We find very intense activity on the helix border over its entire length, going from the bulbar tail to point Zero on the root. The segmental representation follows a proportional and logical distribution in the succession of the segments. Although this study is qualitative in nature, needling is so influential therapeutically that a statistical study would be highly recommended. Conclusion On the basis of clinical evidence, we confirm the postulation of Rene Bourdiol on segmental influence of the helix but propose to extend this action to the entire border of the helix. We find also confirmation for the second postulation of Rene Bourdiol, on the sensory nature of the anterior border and the motor nature of the posterior border. During our investigation however we found also a vascular influence of the cornice (internal hidden border of the helix). On cross section of the helix therefore, we situate three transversal points, cutaneous, motor and vascular, representing the sensory, motor and vascular innervation of the same segmental level. The bulbar thickening of the tail contributes perhaps to a cervical enlargement for the plexus brachialis, but the bulbar tail is much more convincingly identifiable with the medulla oblongata containing the therapeutically interesting spinal trigeminal nucleus and the accessory cuneate nucleus. The localization of the tubercle of Darwin is only present in 10 % of the population. Even when present, the localization of this segmental landmark is too variable and does in my view not represent a lumbosacral enlargement for the innervation of the lower limb as suggested by Bourdiol.

Using Sulforhodamine-101 (SR101) labeling and calcium imaging on in vitro preparations, we investigated the development of spontaneous activity in the spinal enlargements of a marsupial born more immature than eutherian mammals, the opossum Monodelphis domestica. Following the retrograde transport of Calcium Green dye from the limb nerves, we observed the occurrence of spontaneous calcium waves activating the motor columns of the cervical enlargement of opossums aged from P3 to P15 (day of birth: P0) and of the lumbar enlargement from at least P6 to P12. In other preparations, SR101 was added to the bath to identify the active cells. In P1 opossums, only a few SR101-labeled cells were observed in the cervical enlargement and none in the lumbar enlargement. At P5, their number increased cervically and they appeared in the lumbar enlargement. Motoneurons were the major cell type labeled by SR101 but dye leakage made their quantification inaccurate. SR101-labeled cells also occurred elsewhere in the ventral and dorsal grey. Their number increased until P12–14 in both enlargements and then decreased to disappear by P21, the last age examined. Thus in contrast to eutherian mammals, in which spontaneous activity is mostly prenatal, spontaneous activity occurs predominantly postnatally in opossums. It increases at the time when connections from the brain begin to impinge on spinal neurons and when the limbs, especially the hindlimbs, start moving and then decreases as the systems mature.

The rubrospinal tract (RST) of the rat is widely used in studies of regeneration and plasticity, but the electrophysiology of its spinal actions has not been described. In anaesthetised rats with neuromuscular blockade, a tungsten microelectrode was located in the region of the red nucleus (RN) by combining stereotaxis with recording of antidromic potentials evoked from the contralateral spinal cord. Single stimuli through this electrode typically elicited two descending volleys in the contralateral dorsolateral funiculus (DLF) separated by about 1 ms, and one volley recorded from the ipsilateral DLF. Latencies of the ipsilateral and the early contralateral volley were similar. The activation of these volleys depended on the location of the stimulation site in or near the RN. Evidence is adduced to show that: (a) the late contralateral volley is carried by fibres of RST neurones, synaptically activated; (b) the early contralateral volley is mostly carried by RST fibres stimulated directly; (c) the ipsilateral volley is sometimes carried by RST fibres from the RN on the side contralateral to the stimulus; (d) otherwise, either early volley may derive from fibres in other tracts. Synaptic potentials related to the volleys were recorded within the cervical enlargement and their distribution plotted on cross-sections of the spinal cord. These measurements suggest that the great majority of RST terminations are on interneurones in the intermediate region contralateral to the RN. Direct synaptic actions on motoneurones are likely to be weak. Stimulation parameters appropriate for specific activation of the RST in future studies are suggested.

The aim of the present study was to characterize a novel electrophysiological assessment, the magnetically evoked interenlargement response (MIER), by defining the anatomical location of the fast conducting (large myelinated) ascending axons that mediate the response and the relationship between the response and locomotor function following experimental spinal cord injury. Electromyographic (EMG) responses were recorded from the triceps muscles following magnetic stimulation of one hip. Short-latency (approximately 6 ms) EMGs were recorded from triceps muscles in normal controls and following different laceration injuries (dorsal, lateral or dorsal and lateral hemisections) or a 150-kilodyne (kd) contusion injury at the T9 level. The amplitude of the triceps MIER was significantly correlated to the area of spared white matter in the lateral funiculus and to hindlimb function during open field locomotion (r2 = 0.55). Following a complete lateral hemisection, MIERs were present in the triceps bilaterally following stimulation of either hip. Responses could also be recorded from the masseter muscles indicating that the influence of this pathway extends beyond the spinal cord. Anatomical evidence of a bilaterally distributed propriospinal pathway was found when biotinylated dextran amine (BDA) was injected into the lateral white matter on one side of the spinal cord at T9. BDA-labeled axons with varicosities were found bilaterally in the intermediate and ventral gray matter of the caudal region of the cervical enlargement. These observations suggest that MIERs may be useful to quantitatively assess neurotransmission and functional recovery over time after experimental spinal cord injury.

In addition to its projection to the brainstem, the ventral premotor cortex (PMv) sends axons directly to the upper cervical spinal cord in primates, with few terminations more caudally in either the cervical enlargement or in the lumbosacral spinal segments. This finding suggests that PMv plays a role in the control of head movements. Furthermore, comparative neuroanatomical studies indicate that PMv's corticospinal projection was a primate innovation. If the first primates adapted to an arboreal life that involved unimanual feeding, as some experts believe, then perhaps PMv's corticospinal projection evolved to coordinate head movements with this kind of feeding behavior. The computations underlying such control could later be adapted to control head orientation during social signaling.

Transplantation of growth-permissive cells or tissues was used to bridge a lesion cavity and induce axonal growth in experimental spinal cord injury (SCI). Axonal interactions between host and transplant may be affected by upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) following various transplantation strategies. The extent of axonal growth and functional recovery after transplantation of embryonic spinal cord tissue decreases in adult compared to neonatal host. We hypothesized that CSPGs contribute to the decrease in the extent to which transplant supports axonal remodeling and functional recovery. Expression of CSPGs increased after overhemisection SCI in adult rats but not in neonates. Embryonic spinal cord transplant was surrounded by CSPGs deposited in host cord, and the interface between host and transplant seemed to contain a large amount of CSPGs. Intrathecally delivered chondroitinase ABC (C'ase) improved recovery of distal forelimb usage and skilled motor behavior after C4 overhemisection injury and transplantation in adults. This behavioral recovery was accompanied by an increased amount of raphespinal axons growing into the transplant, and raphespinal innervation to the cervical motor region was promoted by C'ase plus transplant. Moreover, C'ase increased the number of transplanted neurons that grew axons to the host cervical enlargement, suggesting that degradation of CSPGs supports remodeling not only of host axons but also axons from transplanted neurons. Our results suggest that CSPGs constitute an inhibitory barrier to prevent axonal interactions between host and transplant in adults, and degradation of the inhibitory barrier can potentiate transplant-mediated axonal remodeling and functional recovery after SCI.

In lumbosacral segments the spinal cord of birds contains numerous paragriseal neurons lying in the white matter of lateral and ventral funiculus. These paragriseal cells project to the cerebellum. Neurons of the dorsal horn (mainly Clarke's column) make up a dorsal spinocerebellar tract and neurons of the ventral horn (mainly spinal border cells) are at the origin of a ventral spinocerebellar tract. It was the aim of this investigation to look for the distribution of spinocerebellar ventral horn neurons and paragriseal cells in the thoracolumbosacral spinal cord of pigeons and to compare this distribution with that of the cervical enlargement. Neuroanatomical tracers were injected into the anterior cerebellum of pigeons and labeled spinal neurons were counted throughout the length of the spinal cord. In the cervical enlargement the number of spinocerebellar ventral horn neurons increases more rostral than that of dorsal horn neurons but the number of both groups of neurons decreases simultaneously at the caudal end of the enlargement. In the ventral horn of thoracolumbosacral segments the number of spinocerebellar ventral horn neurons and paragriseal cells increases again more rostrally than that of dorsal horn cells. However, the number of ventral horn cells decreases whereas that of paragriseal cells and of dorsal horn cells is maintained. This shows that the number of ventral horn cells decreases in favor of paragriseal cells, which supports the suggestion that paragriseal cells are displaced ventral horn spinocerebellar neurons. It is discussed whether the paragriseal neurons migrate toward their input.

The relationship between the activity of pairs of simultaneously recorded spinal interneurons (INs) in the cervical enlargement was studied in five monkeys performing voluntary wrist movements. The tendency for INs to exhibit similar response properties and synchronized firing was tested as a function of physical distance between the cells and their correlational linkages with forearm muscles. Nearby INs tended to have more similar torque and direction turning (signal correlation) and more similar response profiles (e.g., tonic vs phasic firing) than INs that were far apart. This suggests that nearby cells receive common synaptic input. In contrast, the trial-to-trial covariation of rate around the mean rate for all trials (noise correlation) was independent of the distance between the neurons. Furthermore, signal and noise correlation were independent, suggesting different underlying mechanisms. Surprisingly, spike-to-spike correlation between INs was relatively infrequent and weak, as measured by cross-correlation histograms. In contrast, single motor units (SMUs) in forearm muscles fired more synchronously, particularly for SMUs in single extensor muscles. Either common drive to INs is too weak to induce synchronized firing, or there is an active decorrelation mechanism within IN networks.

A 22-year-old man suffered severe sudden onset head and neck pain after being pushed from behind during an assault. Physical examination was normal. Cervical MRI demonstrated an intradural hematoma, anterior to the cord, between C2–4. Subsequent contrast enhanced MR angiography and digital subtraction vertebral angiography confirmed that the cause of the hemorrhage was a fusiform (presumed dissecting) pseudoaneurysm of the artery of the cervical enlargement at its junction with the anterior spinal artery. The aneurysm was managed conservatively. Follow-up angiography demonstrated that the aneurysm had spontaneously thrombosed within 10 days and remained occluded at 2 months. The patient remained occluded at 6 months following the initial injury. Anterior spinal aneurysms represent a management dilemma and options are discussed.

Motor cortex (MCX) motor representation reorganization occurs after injury, learning, and different long-term stimulation paradigms. The neuromodulatory approach of transspinal direct current stimulation (tsDCS) has been used to promote evoked cortical motor responses. In the present study, we used cathodal tsDCS (c-tsDCS) of the rat cervical cord to determine if spinal cord activation can modify the MCX forelimb motor map. We used a finite-element method model based on coregistered high-resolution rat MRI and microcomputed tomography imaging data to predict spinal current density to target stimulation to the caudal cervical enlargement. We examined the effects of cathodal and anodal tsDCS on the H-reflex and c-tsDCS on responses evoked by intracortical microstimulation (ICMS). To determine if cervical c-tsDCS also modified MCX somatic sensory processing, we examined sensory evoked potentials (SEPs) produced by wrist electrical stimulation and induced changes in ongoing activity. Cervical c-tsDCS enhanced the H-reflex, and anodal depressed the H-reflex. Using cathodal stimulation to examine cortical effects, we found that cervical c-tsDCS immediately modified the forelimb MCX motor map, with decreased thresholds and an expanded area. c-tsDCS also increased SEP amplitude in the MCX. The magnitude of changes produced by c-tsDCS were greater on the motor than sensory response. Cervical c-tsDCS more strongly enhanced forelimb than hindlimb motor representation and had no effect on vibrissal representation. The finite-element model indicated current density localized to caudal cervical segments, informing forelimb motor selectivity. Our results suggest that c-tsDCS augments spinal excitability in a spatially selective manner and may improve voluntary motor function through MCX representational plasticity.

The electrophysiological investigation of neurones located in the cervical enlargement of the spinal cord was performed in eight-chloralose anaesthetized cats. Neurones were recorded intracellularly or extracellularly and identified by antidromic stimulation. The main purpose of the study was to test whether these neurones give off collateral branches ascending to the inferior cerebellar peduncle and descending to the sacral segments (S1/S2). Recordings were made from 78 neurones located in medial and central parts of Rexed's laminae VII and VIII of C6/C7 segments. Four subpopulations could be distinguished from their patterns of propriospinal or supraspinal projections: (a) ascending/descending neurones with axons ascending to RB and descending to S1/S2 (23%); (b) ascending/descending neurones projecting to RB and the level of Th13 (14%); (c) propriospinal neurones descending to Th13 (15%); (d) propriospinal neurones descending to S1/S2 (48%). Within these groups, ipsilateral, contralateral and bilateral descending projections were observed. The mean axonal conduction velocities for descending and ascending collaterals of bidirectional neurones were 59 and 39 m/s, respectively. Results suggest that parallel transmission of information to supraspinal and spinal centres plays an important role in the process of movement coordination.

Activated microglia is associated with neurodegenerative processes, but the precise role of this cell population is difficult to identify. Most experimental models employed to examine microglial responses involve acute alterations of neuronal integrity, in contrast to the progressive nature of neurodegenerative diseases. In order to approach the clinical situation better, the microglial response was analyzed in the murine mutant wobbler, which exhibits a well-characterized neurodegenerative pathology, manifested by motoneuronal death following a period of cellular dysfunction with characteristic morphological features. Microglial cells were identified using anti-Mac1 or anti-IgG antibodies. Examination of the changes in density, localization, and phenotype of microglia differentiated two types of responses in wobblers. A first type of response was observed as early as in the third week after birth, when the only apparent neuronal defect was the morphological alteration of a subset of motoneurons in the cervical spinal cord, which was maintained later on. The activated microglia extended long processes that selectively ensheathed vacuolated motoneurons. At later stages, when motoneuron death became prominent, an additional type of response was characterized by an increased density of reactive microglia that was seen extending throughout the cervical enlargement. This secondary microglial response occurred in parallel to the infiltration of T-lymphocytes. Thus, these results point to a differential response of microglial cells to a progressive neurodegenerative process.

Study design: We have applied conventional histochemical and morphometric techniques to study the changes within the human spinal `hand' motor neuron pool after spinal cord injury in patients who presented with acute traumatic central cord syndrome (ATCCS). Objective: To determine whether a reduction of large alpha motor neurons at the C7, C8 and T1 spinal cord levels underlies the mechanism which causes hand dysfunction seen in patients with (ATCCS). Background: The etiology of upper extremity weakness in ATCCS is debated and injury and/or degeneration of motor neurons within the central gray matter of the cervical enlargement has been advanced as one potential etiology of hand weakness. Methods: The spinal cords of five individuals with documented clinical evidence of ATCCS and three age-matched controls were obtained. The ATCCS spinal cords were divided into acute/sub-acute (two cases) and chronic (three cases) groups depending on the time to death after their injury; the chronic group was further subdivided according to the epicenter of injury. We counted the motor neurons using light microscopy in 10 randomly selected axial sections at the C7, C8 and T1 spinal cord levels for each group. We also analyzed the lateral and ventral corticospinal tracts (CST) in all groups for evidence of Wallerian degeneration and compared them to controls. Results: A primary injury to the lateral CST was present in each case of ATCCS with evidence of Wallerian degeneration distal to the epicenter of injury. There was minimal Wallerian degeneration within the ventral corticospinal tracts. In the chronic low cervical injury group, there was a decrease in motor neurons supplying hand musculature relative to the other injury groups where the motor neurons sampled at the time of death were not reduced in number when compared to the control group. Conclusions: We hypothesize that hand dysfunction in ATCCS can be observed after spinal cord injury without any apparent loss in the number of motor neurons supplying the hand musculature as seen in our acute/sub-acute (n=2) and our chronic high injury (n=1) groups. The motor neuron loss seen in the chronic low level injury was felt to be secondary to the loss of C7, C8, and T1 neurons adjacent to the injury epicenter.

The organization of spinocerebellar tract (SCT) neurons in the chicken was studied quantitatively using retrograde wheat germ agglutinin-horseradish peroxidase labelling. The chicken spinal cord was divided into five regions based on the distribution of SCT neurons: the cervical region (the spinal segments [SS], 1–12, which contained 32% of the total number of SCT neurons), the cervical enlargement (SS13–15, 13.4%), the thoracic region (SS16–20, 13%), the thoraco-lumbosacral region (SS21–26, 34.6%), and the posterior lumbosacral region (SS27–30, 7%). Clarke’s column was found in two regions, a cervical one (SS12–16) and a lumbar one (SS21–28). The spinal border cells were less numerous and also present in two parts, a cervical one (SS10–15) and a caudal one (SS20–24). SCT neurons of the ventral part of the ventral horn were found in the cervical enlargement and SS16 (lamina VIII), and in the thoraco- and posterior lumbosacral regions (laminae VIII and IX). The ventral marginal nucleus consisted exclusively of SCT neurons but the major and minor marginal nuclei did not contain SCT neurons. In the cervical region most of SCT neurons were observed in the ventral horn, while the central cervical nucleus, which consists of SCT neurons in mammals, was not identified in the chicken.

Neck sensory information is important for control of head and body movements in all vertebrates. Neuroanatomic tracing methods were used to study the pathways of neck afferent systems. Both the projection of primary afferent fibers and of secondary afferent pathways to brainstem and cerebellum were investigated with the anterograde transport of dextran amines as tracers (biotinylated dextran amine and tetramethyl rhodamine dextran amine). For comparison, the projections of spinocerebellar systems of wing and leg were studied also. Complementary experiments using retrograde tracers (Fast Blue, tetramethyl rhodamine dextran amine, rhodamine isothiocyanate) injected into the cerebellum served to corroborate the results of the anterograde tracing experiments. Primary neck afferent fibers terminated in the spinal gray substance with dense terminal fields in laminae I to V of the dorsal horn and lamina IX of the ventral horn as well as in the marginal nuclei located at the lateral border of the spinal cord. In the brainstem, dense terminal fields were seen in deep layers of the medullary dorsal horn, in the external cuneate nucleus, and in group x. Secondary neck afferents arising from ventral horn cells showed a significant projection to the descending and medial vestibular nuclei and to the medial cerebellar nucleus. Terminals were found both in the anterior and the posterior cerebellum. A quantitative evaluation disclosed that most terminals of neck afferents distributed in lobules II-IV of the anterior cerebellum and lobule IX of the posterior cerebellum. With injections aimed at spinocerebellar neurons located into the cervical and lumbosacral enlargements, no projections were found in the vestibular or deep cerebellar nuclei. Projections from the cervical enlargement were concentrated in lobules III-V and those from the lumbosacral enlargement in lobules III-VI. This points to a rostrocaudal somatotopic representation of neck, wing, and leg in the anterior cerebellum. The results of the retrograde tracing experiments support such a somatotopic organization.

Spinoreticular neurons projecting to the lateral reticular nucleus (LRN) were investigated electrophysiologically in the cervical enlargement of the cat spinal cord. Experiments were performed on alpha-chloralose anaesthetized animals. Antidromic action potentials were recorded extracellularly from cells located in C6 and C7 segments following stimulation of the ipsilateral LRN. The total sample included 50 neurons. Their cell bodies were found to be distributed in Rexed's laminae VI-VIII of the gray matter. Axonal conduction velocities ranged from 14.7 to 89.7 ms-1. Considerable differences between particular cases enabled two separate groups of slower and faster conduction to be distinguished. Values for these two groups were 14.7-44.3 ms-1 and 52.2-89.7 ms-1, respectively. Discrete differences with regard to the location of these groups were also pointed out. Such differentiation suggests that a proportion of axons from the slower conducting pool may be in fact collaterals of neurons that project to other brainstem centers or to lower levels of the spinal cord.

Nitric oxide (NO) possibly plays an important role in the events resulting in hyperalgesia. Nitric oxide synthase (NOS) is a key enzyme in the production of NO. In this study, the relationship between NOS and hyperalgesia in a rat chronic arthritis model was tested. Chronic arthritis was induced by injection of incomplete Freund's adjuvant into the knee joint cavity unilaterally. The paw withdrawal latency (PWL) to radiant heat was used to detect secondary thermal hyperalgesia induced by the arthritis. After 1 day the PWL of the arthritic hind-paw decreased and it reached its nadir at 3 days after induction of arthritis. The lumbar and cervical enlargement of the spinal cord were removed in different groups of animals 3, 7, 14, or 21 days after induction of arthritis, and frozen tissue sections were cut. Two series of sections were incubated with polyclonal antibodies to neuronal NOS (nNOS) or to inducible NOS (iNOS). nNOS was found to increase gradually in laminae I-III in the lumbar but not in the cervical enlargement. The change became most obvious 14 days after induction of arthritis as compared to the control animals. Ependymal cells around the central canal of the lumbar enlargement were more densely stained by anti-iNOS after arthritis. A corresponding change was also found in the cervical enlargement. Computer-assisted image analysis revealed that the mean density of the affected areas in the treated group increased significantly compared with the control animals. This study suggests that the expression of both nNOS and iNOS increase following induction of chronic arthritis, which in turn would presumably lead to an increase in the production of NO. This process could be involved in mediation of the secondary thermal hyperalgesia induced by chronic arthritis.