Section Of Cord Research Articles

Proliferative activity and motoneurone recruitment persist at the spinal cord central canal during larval and some postlarval stages in the rainbow trout (Oncorhynchus mykiss).

We previously found a linear relationship between the cross sectional myotomal area and the motoneurone number in the growing trout during postlarval stages. These neurones increased in number until a fish length of 150 mm, which prompted us to examine how motor neurones are recruited afterwards to meet the growth of their target myotomal muscle. Young adult (260 mm in length), fingerlings (F, 120-170 mm), fry (Fr, 70 mm) and eleutherembryos (Es, 20-30 mm) of rainbow trout (Oncorhyncus mykiss) were employed in this study. PCNA immunohistochemistry was used for monitoring the proliferative activity in the epithelium of the spinal cord central canal. This activity was quantified as the number of PCNA labelled cells for each spinal cord section. In Es and Fry, a mean value of 3-5 labelled cells for each section was found with a sharp decrease in young F (120 mm long). After this fish length, it was not possible to quantitatively evaluate the proliferative activity at the central canal. However, labelled cells were seldom found in the spinal cord sections until a fish length of 260 mm. From these data it is possible to conclude that motoneurone recruitment in the trout spinal cord is down-regulated at the F stage. Afterwards, we found that motoneurones increase in size to meet the growth of their target myotomal muscle.

Function Recovery after Transplantation of Fetal Brain Tissue into Injured Spinal Cord in Experimental Rats

Rakei, S.M., Rahmanian, A., Saffarian, A., Shafeian, R. and Mehrabani, D. 2009. Function recovery after transplantation of fetal brain tissue into injured spinal cord in experimental rats. J. Appl. Anim. Res., 36: 303–306. To determine the effect of transplantation of fetal brain tissue on regeneration of injured spinal cord and the limb function recovery, forty 30-week old male Sprague-Dawley 350–450 g rats were randomly and equally divided into two groups. In 5 pregnant rats the fetuses were removed and the embryonic brain tissues were sectioned into 0.05 mm segments under microscope. The vertebral column was exposed and a 0.1 mm segment of spinal cord medulla at the T10-T11 level was completely dissected in all rats of both groups. A 0.05 mm segment of rat fetus brain was implanted into the injured section of spinal cord of all rats in the case group. No further intervention was done in the control group. After 24 h lower extremity paraplegia was confirmed in all rats. After six weeks, no locomotor improvement was seen in the control group (Basso-Beattie-Bresnahan locomotor rating scale, BBB=0). 15% of rats in the case group had some degrees of recovery from spinal cord injury. Our findings suggest that fetal neural transplants could potentially be an effective surgical intervention for treatment of SCI even though more investigations are warranted.

Succinylcholine-induced Hyperkalemia and Beyond

The mechanism of succinylcholine-induced hyperkalemia was studied in three lesions affecting canine gastrocnemius muscle. Dogs were treated for 1 month before study: 10 with normal activity, 5 with unilateral sciatic nerve section, active on 3 legs, 5 with unilateral cast immobilization of a hind limb and pelvis, active on 3 legs, and 7 inactive with T6 section of the spinal cord. Succinylcholine responses were determined during thiopental―ha lothane (mean expired halothane 1.0 ± 0.2%) endotracheal anesthesia with arterial carbon dioxide tension of 38—42 mmHg, arterial oxygen tension of 100—120 mmHg, and muscle and body temperatures maintained at 37° ± 0.2°C. The investigators isolated and collected the venous drainage of gastrocnemius muscle and measured its total blood flow. Muscle potassium release and oxygen consumption were calculated as blood flow x (arterial content — venous content). Succinylcholine-induced gastrocnemius potassium release was greatest after both sciatic and cord section; oxygen consumption was increased in parallel. Disuse atrophy of one leg slightly increased both values but was insufficient to produce systemic hyperkalemia. Reuptake of potassium followed succinylcholine-induced release. Given before succinylcholine, modest doses of gallamine slightly modified the release of potassium, and total paralysis by gallamine blocked it.

SURGICAL MANAGEMENT OF SPINAL CATHETER GRANULOMAS

Spinal catheter granulomas are a rare and, most likely, underreported complication of intrathecal opioid therapy. Such granulomas can be associated with devastating neurological sequelae if not treated in a timely fashion. Most neurosurgeons, however, are unlikely to have had experience in the surgical management of this condition. The authors present 3 surgical cases of patients with spinal catheter granulomas with neurological deficits. One patient's intraoperative video illustrates the challenges of diagnosis, radiological assessment, and surgery for spinal catheter granulomas. All 3 patients had implanted opioid pumps for management of chronic spinal pain secondary to fracture, tethered cord, and back pain. Increasing back pain and a progressive myelopathy was observed in all patients. A clear radiological diagnosis was made more difficult because of instrumentation artifact in 1 case and claustrophobia in another. Computed tomographic myelography was necessary in 1 case. The surgical findings were: 1 extradural catheter with granuloma and 2 intradural catheters encased with granuloma and adherent to the cord. The extradural catheter was trimmed of granuloma and replaced intradurally in 1 case. The patients with intradural catheter granulomas required judicious dissection of the granulomas from the dorsum of the cord, duroplasty, and catheter section. Critical intraoperative stages were recorded and are presented in digital movie format. Two patients had neurological improvement after surgery; however, 1 patient remained paraplegic. The 2 patients with catheter section required opioid withdrawal treatment. The operative management of spinal intrathecal granulomas associated with opioid infusion pumps can be challenging and depends on a high degree of clinical suspicion, imaging results, and operative findings.

Surgery Induces Cyclooxygenase-2 Expression in the Rat Cervical Spinal Cord

Nonsteroidal anti-inflammatory drugs with a selective cyclooxygenase-2 (COX-2) inhibitory profile are effective analgesics in the postoperative period. This implies that surgery induces COX-2 biosynthesis. We examined whether peripheral surgical trauma can induce COX-2 expression in the rat cervical spinal cord. Sprague-Dawley rats were divided into 2 groups. The control group underwent general anesthesia but had no surgery. The surgical group underwent general anesthesia and surgical exposure of neck structures. After 14 days, the animals were euthanized, and a section of cervical spinal cord was taken to identify COX-1 and COX-2 expression by immunohistochemical analysis. Two independent blinded observers analyzed the slides. Analysis of COX-1 protein expression revealed homogenous staining in glial cells in all regions of the cervical spinal cord examined. There was no difference in expression between the control and surgical groups. However, whereas the control group demonstrated minimal COX-2 expression, the surgical group showed extensive neuronal and glial cell cytoplasmic COX-2 expression. This study demonstrates that surgery induces COX-2 expression in the rat cervical spinal cord. This could provide a scientific rationale for the use of selective COX-2 inhibitors as analgesics in the postoperative period.

Primary Progressive Multiple Sclerosis: Tactile-associated Functional MR Activity in the Cervical Spinal Cord

To assess the extent of tactile-associated cervical spinal cord activation in patients with primary progressive (PP) multiple sclerosis (MS) and to investigate the relationship between spinal cord functional activation and the severity of cervical spinal cord and brain structural damage by using magnetic resonance (MR) images. The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Cervical spinal cord functional MR images were obtained in 23 patients with PP MS and 18 healthy control subjects during tactile stimulation of the right hand. Conventional and diffusion-tensor MR images of the brain and spinal cord were also acquired. Mean stimulus-related signal intensity change for all activated voxels and the distribution of functional MR activity at each spinal cord level were obtained. Univariate analysis was used to compare MR findings between groups. Between-group differences in topographic distribution of functional MR activity were evaluated by using random-effects logistic regression models. Patients with PP MS had higher mean spinal cord activity on functional MR images than did controls. A higher occurrence of functional MR activation in the right versus left side of the spinal cord and in the posterior versus anterior section of the spinal cord was found in both control subjects and patients with PP MS. Patients who were mildly disabled had a pattern of functional MR activity distribution similar to that of controls, but patients who were more severely disabled did not show differential activation between the right and left sides of the spinal cord. A higher occurrence of functional MR activity in the anterior section of the right side of the spinal cord at the level of the C6-7 intervertebral disk (P = .05) and the left side of the spinal cord at the level of the C7-T1 intervertebral disk (P = .03) was found in patients with PP MS than in control subjects. Mean spinal cord functional MR imaging signal intensity change correlated with spinal cord fractional anisotropy. Patients with PP MS showed tactile-associated cervical spinal cord overactivation. Spinal cord functional changes, possibly owing to injured interneurons, likely contribute to the complex process that leads to the accumulation of irreversible disability in patients with PP MS.

Assessment of spinal somatosensory systems with diffusion tensor imaging in syringomyelia

Objective:The use of diffusion tensor imaging with three-dimensional fibre tracking (DTI-FT) was tested for the assessment of spinal sensory tract lesions. The relationships between tract lesions quantified with DTI-FT were...

Lactobacillus farciminis treatment attenuates stress‐induced overexpression of Fos protein in spinal and supraspinal sites after colorectal distension in rats

Abstract Irritable bowel syndrome (IBS), frequently associated with psychological distress, is characterized by hypersensitivity to gut wall distension. Some probiotics are able to alleviate IBS symptoms and reduce visceromotor response to mechanical stimuli in animals. Moreover, we have previously shown that Lactobacillus farciminis treatment abolished the hyperalgesia to colorectal distension (CRD) induced by acute stress. The aims of the present study were to determine whether (i) stress-induced visceral hyperalgesia modifies the expression of Fos, a marker of general neuronal activation, induced by CRD, (ii) this activation can be modulated by L. farciminis treatment. Female rats were treated by L. farciminis and CRD was performed after partial restraint stress (PRS) or sham-PRS. The expression of Fos protein was measured by immunohistochemistry. After CRD or PRS, Fos expression was increased in spinal cord section (S1), nucleus tractus solitarius (NTS), paraventricular nucleus (PVN) of the hypothalamus, and in the medial nucleus of the amygdala (MeA). The combination of both stimuli, PRS and CRD, markedly increased this Fos overexpression in the sacral spinal cord section, PVN and MeA, but not in NTS. By contrast, a pretreatment with L. farciminis significantly reduced the number of Fos positive cells in these area. This study shows that PRS enhances Fos protein expression induced by CRD at the spinal and supraspinal levels in rats. Lactobacillus farciminis treatment inhibited this enhancing effect, suggesting that the antinociceptive effect of this probiotic strain results from a decrease of the stress-induced activation/sensitization of sensory neurons at the spinal and supraspinal level.

Effects of White, Grey, and Pia Mater Properties on Tissue Level Stresses and Strains in the Compressed Spinal Cord

Recent demographics demonstrate an increase in the number of elderly spinal cord injury patients, motivating the desire for a better understanding of age effects on injury susceptibility. Knowing that age and disease affect neurological tissue, there is a need to better understand the sensitivity of spinal cord injury mechanics to variations in tissue behavior. To address this issue, a plane-strain, geometrically nonlinear, finite element model of a section of a generic human thoracic spinal cord was constructed to model the response to dorsal compression. The material models and stiffness responses for the grey and white matter and pia mater were varied across a range of reported values to observe the sensitivity of model outcomes to the assigned properties. Outcome measures were evaluated for percent change in magnitude and alterations in spatial distribution. In general, principal stresses (114-244% change) and pressure (75-119% change) were the outcomes most sensitive to material variation. Strain outcome measures were less sensitive (7-27% change) than stresses (74-244% change) to variations in material tangent modulus. The pia mater characteristics had limited (<4% change) effects on outcomes. Using linear elastic models to represent non-linear behavior had variable effects on outcome measures, and resulted in highly concentrated areas of elevated stresses and strains. Pressure measurements in both the grey and white matter were particularly sensitive to white matter properties, suggesting that degenerative changes in white matter may influence perfusion in a compressed spinal cord. Our results suggest that the mechanics of spinal cord compression are likely to be affected by changes in tissue resulting from aging and disease, indicating a need to study the biomechanical aspects of spinal cord injury in these specific populations.

Matrix Metalloproteinase-12 Deficiency Worsens Relapsing-Remitting Experimental Autoimmune Encephalomyelitis in Association with Cytokine and Chemokine Dysregulation

The elevation of several members of the matrix metalloproteinase (MMP) family promotes the pathophysiology of both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Nonetheless, given the multiple activities of MMPs, it remains possible that increased levels of a particular MMP may have beneficial functions during disease progression. We reported previously that MMP-12(-/-) mice of the 129/SvEv strain had a poorer EAE outcome than wild-type controls. However, we did not determine further differences in disease profiles between these groups. Using the EAE model in 129/SvEv mice, we report that disease in both wild-type and MMP-12(-/-) mice follows a relapsing-remitting course. Although both mouse groups had similar clinical onsets, subsequent relapses were more severe in MMP-12(-/-) mice; their residual disability at remission was also higher compared with wild-type controls. The worsened relapses and remissions in MMP-12(-/-) mice occurred despite a deficiency of the antigen recall capacity of lymph node-derived cells as well as a reduction in the proportion of macrophages in the spinal cord during the chronic phase of EAE. Significantly, large increases of levels of chemokines and cytokines were found in the spinal cords of MMP-12(-/-) mice during chronic EAE. These results highlight MMP-12 as a beneficial enzyme in EAE and suggest that therapeutic interventions in multiple sclerosis should avoid targeting MMP-12.

Impairment of postural control in rabbits with extensive spinal lesions.

Our previous studies on rabbits demonstrated that the ventral spinal pathways are of primary importance for postural control in the hindquarters. After ventral hemisection, postural control did not recover, whereas after dorsal or lateral hemisection it did. The aim of this study was to examine postural capacity of rabbits after more extensive lesion (3/4 section of the spinal cord at T(12) level), that is, with only one ventral quadrant spared (VQ animals). They were tested before (control) and after lesion on the platform periodically tilted in the frontal plane. In control animals, tilts of the platform regularly elicited coordinated electromyographic (EMG) responses in the hindlimbs, which resulted in generation of postural corrections and in maintenance of balance. In VQ rabbits, the EMG responses appeared only in a part of tilt cycles, and they could be either correctly or incorrectly phased in relation to tilts. Because of a reduced value and incorrect phasing of EMG responses on both sides, this muscle activity did not cause postural corrective movements in the majority of rabbits, and the body swayed together with the platform. In these rabbits, the ability to perform postural corrections did not recover during the whole period of observation (< or =30 days). Low probability of correct EMG responses to tilts in most rabbits as well as an appearance of incorrect responses to tilts suggest that the spinal reflex chains, necessary for postural control, have not been specifically selected by a reduced supraspinal drive transmitted via a single ventral quadrant.

State of the cervical section of the spinal cord in patients with remitting multiple sclerosis during immunomodulatory treatment

MRI scans were obtained of the cervical section of the spinal cords of 30 patients with remitting multiple sclerosis. During the study period, patients received immunomodulatory agents (seven received interferon beta-1a, 13 received interferon beta-1b, and 10 received glatiramer acetate). Total focus volume in brain matter was assessed before and after treatment, along with the linear size of the spinal cord on sagittal sections at the level of the inferior margin of the body of C2. There was a significant (p = 0.002) reduction in focus volume in the group overall, from 10993 mm(3) (8098-13888 mm(3), p < 0.05; Me = 9336) to 5630 mm(3) (7400-3860 mm(3), p < 0.05, Me = 4180). There were also significant decreases in focus volume on the background of treatment with interferon beta-1b and glatiramer acetate (p = 0.026 and 0.027, respectively). Significant differences between groups were found in the magnitudes of increases in spinal cord atrophy: H (2, n = 30) = 8.06; p = 0.0178. Patients given glatiramer acetate showed a significantly smaller increase in atrophy as compared with those treated with interferon beta (p < 0.02).

Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: Wind-up mechanisms

With the exception of one monkey’s study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat’s SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that Aδ information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3–1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3–4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.

The automatic bladder, excessive sweating and some other reflex conditions, in gross injuries of the spinal cord. By Henry Head, MD, FRS and George Riddoch, MD, Captain, Royal Army Medical Corps. (Officer in charge of the Empire Hospital, Vincent Square). Brain 1917; 40: 188-263.

‘The present War has afforded innumerable opportunities for investigating the phenomena due to gross injuries of the spinal cord …’. After working independently on the manifestations of total transverse section and the explanation for excess sweating as a sequel to spinal cord injury, respectively, Dr Head and Captain Riddoch (Figs 1 and 2) now realize that, in also studying the functional capacity of the automatic bladder, they are looking at different aspects of the same problem; and so they join forces. Based at the London Hospital and the Empire Hospital for Officers, they propose a physiological explanation for the clinical observations made by Dr Riddoch (see Brain 1917; 40: 264–402 and 2004; 129: 2150); and offer a general explanation for the remarkable behaviour of the distal end of the severed spinal cord. They acknowledge the invaluable work of the Cambridge school of physiology (John Langley, [Sir] Hugh Anderson and Thomas [TR] Elliot inter alia ) on the involuntary nervous system (summarized and reviewed in the same issue by Dr EG Fearnsides, Brain 1917; 40: 149–87). Fig. 1 Dr Henry Head (1861–1940). Fig. 2 Dr George Riddoch (1888–1847). Acute cord section results in urinary retention and, if complicated by infection and bed-sores, carries a high early mortality. After 2–3 weeks—sooner with partial cord injury and later when there is concomitant damage to the cauda equina—survivors usually develop automatic bladder emptying. Head and Riddoch aim to show that this partially restored function and other reflex activities to be discussed, depend on extra-vesical stimuli. First, in chronic but stable cases, they measure the capacity of the gently distended bladder and show that, in Case 1 studied at 158 days, small oscillations causing slight increases of pressure are seen immediately that increase in amplitude at volumes greater than 400 ml until complete reflex voiding occurs in three phases at …

Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input

We investigated the role of afferent information during recovery of coordinated rhythmic activity of the hindlimbs in rats with a complete spinal cord section (approximately T8) and unilateral deafferentation (T12-S2) to answer the following questions: (1) Can bilateral stepping be generated with only afferent projections intact on one side? (2) Can the sensory input from the non-deafferented side compensate for the loss of the afferent input from the deafferented side through the crossed connections within the lumbosacral spinal cord? (3) Which afferent projections to the spinal cord from the non-deafferented side predominantly mediate the effect of epidural stimulation to facilitate stepping? Recovery of stepping ability was tested under the facilitating influence of epidural stimulation at the S1 spinal segment, or epidural stimulation plus quipazine, a 5-HT agonist. All chronic spinal rats were able to generate stepping-like patterns on a moving treadmill on the non-deafferented, but not deafferented, side from 3 to 7 weeks after surgery when facilitated by epidural stimulation. Adaptation to the loss of unilateral afferent input was evident at 7 weeks after surgery, when some movements occurred on the deafferented side. Spinal-cord-evoked potentials were observed on both sides, although middle (monosynaptic) and late (long latency) responses were more prominent on the non-deafferented side. The afferent information arising from the non-deafferented side, however, eventually could mediate limited restoration of hindlimb movements on the deafferented side. These data suggest that facilitation of stepping with epidural stimulation is mediated primarily through ipsilateral afferents that project to the locomotor networks.

Enrichment of C-Terminal Fragments in TAR DNA-Binding Protein-43 Cytoplasmic Inclusions in Brain but not in Spinal Cord of Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

TAR DNA-binding protein (TDP-43) has been recently described as a major pathological protein in both frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. However, little is known about the relative abundance and distribution of different pathological TDP-43 species, which include hyperphosphorylated, ubiquitinated, and N-terminally cleaved TDP-43. Here, we developed novel N-terminal (N-t) and C-terminal (C-t)-specific TDP-43 antibodies and performed biochemical and immunohistochemical studies to analyze cortical, hippocampal, and spinal cord tissue from frontotemporal dementia with ubiquitin-positive inclusions and amyotrophic lateral sclerosis cases. C-t-specific TDP-43 antibodies revealed similar abundance, morphology, and distribution of dystrophic neurites and neuronal cytoplasmic inclusions in cortex and hippocampus compared with previously described pan-TDP-43 antibodies. By contrast, N-t-specific TDP-43 antibodies only detected a small subset of these lesions. Biochemical studies confirmed the presence of C-t TDP-43 fragments but not extreme N-t fragments. Surprisingly, immunohistochemical analysis of inclusions in spinal cord motor neurons in both diseases showed that they are N-t and C-t positive. TDP-43 inclusions in Alzheimer's disease brains also were examined, and similar enrichment in C-t TDP-43 fragments was observed in cortex and hippocampus. These results show that the composition of the inclusions in brain versus spinal cord tissues differ, with an increased representation of C-t TDP-43 fragments in cortical and hippocampal regions. Therefore, regionally different pathogenic processes may underlie the development of abnormal TDP-43 proteinopathies.

Central Delivery of Dicer-substrate siRNA: A Direct Application for Pain Research

RNA interference (RNAi) is gaining acceptance as a potential therapeutic strategy against peripheral disease, and several clinical trials are already underway with 21-mer small-interfering RNA (siRNA) as the active pharmaceutical agent. However, for central affliction like pain, such innovating therapies are limited but nevertheless crucial to improve pain research and management. We demonstrate here the proof-of-concept of the use of 27-mer Dicer-substrate siRNA (DsiRNA) for silencing targets related to CNS disorders such as pain states. Indeed, low dose DsiRNA (0.005 mg/kg) was highly efficient in reducing the expression of the neurotensin receptor-2 (NTS2, a G-protein-coupled receptor (GPCR) involved in ascending nociception) in rat spinal cord through intrathecal (IT) administration formulated with the cationic lipid i-Fect. Along with specific decrease in NTS2 mRNA and protein, our results show a significant alteration in the analgesic effect of a selective-NTS2 agonist, reaching 93% inhibition up to 3-4 days after administration of DsiRNA. In order to ensure that these findings were not biased by unsuspected off-target effects (OTEs), we also demonstrated that treatment with a second NTS2-specific DsiRNA also reversed NTS2-induced antinociception, and that NTS2-specific 27-mer duplexes did not alter signaling through NTS1, a closely related receptor. Altogether, DsiRNAi represents a potent tool for dissecting nociceptive pathways and could further lead to a new class of central active drugs.

Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis

Functional MRI (fMRI) was used to assess proprioceptive-associated cervical cord activity in 24 relapsing multiple sclerosis (MS) patients and 10 controls. Cord and brain conventional and diffusion tensor (DT) MRI were also acquired. fMRI was performed using a block design during a proprioceptive stimulation consisting of a passive flexion-extension of the right upper limb. Cord lesion number, cross-sectional area, mean diffusivity (MD) and fractional anisotropy (FA), whole brain and left corticospinal tract lesion volume (LV), gray matter (GM) MD, and normal-appearing white matter (NAWM) MD and FA were calculated. MS patients had higher average cord fMRI signal changes than controls (3.4% vs. 2.7%, P = 0.03). Compared to controls, MS patients also had a higher average signal change in the anterior section of the right cord at C5 (P = 0.005) and left cord at C5-C6 (P = 0.03), whereas no difference was found in the other cord sections. Cord average signal change correlated significantly with cord FA and brain left corticospinal tract LV, GM-MD, and NAWM-FA. This study shows an abnormal pattern of activations in the cervical cord of MS patients following proprioceptive stimulation. Cord fMRI changes might have a role in limiting the clinical consequences of MS associated with irreversible tissue damage.

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: Effects of an antibody treatment neutralizing Nogo-A

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

Modifications of Locomotor Pattern Underlying Escape Behavior in the Lamprey

Two forms of undulatory locomotion in the lamprey (a lower vertebrate) have been described earlier: fast forward swimming (FFS) used for long distance migrations and slow backward swimming (SBS) used for escape from adverse tactile stimuli. In the present study, we describe another form of escape behavior: slow forward swimming (SFS). We characterize the kinematic and electromyographic patterns of SFS and compare them with SBS and FFS. The most striking feature of SFS is nonuniformity of shape and speed of the locomotor waves propagating along the body: close to the site of stimulation, the waves slow down and the body curvature increases several-fold due to enhanced muscle activity. Lesions of afferents showed that sensory information critical for elicitation of SFS is transmitted through the dorsal roots. In contrast, sensory signals that induce SBS are transmitted through the dorsal roots, lateral line nerves, and trigeminal nerves. Persistence of SFS and SBS after different lesions of the spinal cord suggests that the ascending and descending pathways, necessary for induction of SBS and SFS, are dispersed over the cross section of the spinal cord. As shown previously, during FFS (but not SBS) the lamprey maintains the dorsal-side-up body orientation due to vestibular postural reflexes. In this study we have found that the orientation control is absent during SFS. The role of the spinal cord and the brain stem in generation of different forms of undulatory locomotion is discussed.