Pathways In Spinal Cord Research Articles

The effect of chronic undernourishment on the synaptic depression of cutaneous pathways in the rat spinal cord

The aim of this study was to determine the effect of chronic undernourishment on the amplitude depression of the first negative component in the cord dorsum potentials (N(1)-CDPs) caused by the conditioning stimulation of sensory cutaneous nerves in the rat spinal cord. Single electrical pulses (1Hz; 2 times threshold) applied to the sural (SU) nerve of control rats (n=14) produced CDPs with a first negative component (N(1)-CDPs) larger in amplitude (14.2±1.3%, p<0.01) than those recorded in chronically undernourished rats (n=14; 3 times threshold). The conditioning stimulation of the SP nerve (4 shocks at 300Hz, 3×T) in the control rats (n=5) evoked a long-lasting (~200ms) depression of the N(1)-CDP (60.2±7.2%). In contrast such depression was smaller in magnitude (42.5±5.7%, p<0.01) and time course (100-120ms) in undernourished rats (n=7). The systemic application of picrotoxin (PTX) reduced, but did not abolish the conditioned depression of the N(1)-CDPs and DRPs in both the control and undernourished rats. By assuming that the depression of the N(1)-CDPs is representative of presynaptic mechanisms, it is proposed that chronic undernourishment influence the activation of presynaptic neuronal pathways that regulate the transmitter release of cutaneous afferent fibers in the spinal cord and such effect could act as a compensatory mechanism that counterbalances the decreased activation of spinal neurons by the reduced afferent input in the rat.

Erythropoietin effect on sensorimotor recovery after contusive spinal cord injury: An electrophysiological study in rats

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. It has been shown in rats that the acute administration of recombinant human erythropoietin (rhEPO) following a contusive SCI improves the recovery of hindlimb motor function, as measured with the locomotor BBB (Basso, Beattie, Bresnahan) scale. This scale evaluates overall locomotor activity, without testing whether the rhEPO-induced motor recovery is due to a parallel recovery of sensory and/or motor pathways. Aim of the present study was to utilize an electrophysiological test to evaluate, in a rat model of contusive SCI, the transmission of both ascending and descending pathways across the damaged cord at 2, 5, 7, 11, and 30days after lesion, in animals treated with rhEPO (n=25) vs saline solution (n=25). Motor potentials evoked by epicortical stimulation were recorded in the spinal cord, and sensory-evoked potentials evoked by spinal stimulation were recorded at the cortical level. In the same animals BBB score and immunocytochemical evaluation of the spinal segments caudal to the lesion were performed. In rhEPO-treated animals results show a better general improvement both in sensory and motor transmission through spared spinal pathways, supposedly via the reticulo-spinal system, with respect to saline controls. This improvement is most prominent at relatively early times. Overall these features show a parallel time course to the changes observed in BBB score, suggesting that EPO-mediated spared spinal cord pathways might contribute to the improvement in transmission which, in turn, might be responsible for the recovery of locomotor function.

Traumatology of the optic nerve and contribution of crystallins to axonal regeneration

Within a few decades, the repair of long neuronal pathways such as spinal cord tracts, the optic nerve or intracerebral tracts has gone from being strongly contested to being recognized as a potential clinical challenge. Cut axonal stumps within the optic nerve were originally thought to retract and become irreversibly necrotic within the injury zone. Optic nerve astrocytes were assumed to form a gliotic scar and remodelling of the extracellular matrix to result in a forbidden environment for re-growth of axons. Retrograde signals to the ganglion cell bodies were considered to prevent anabolism, thus also initiating apoptotic death and gliotic repair within the retina. However, increasing evidence suggests the reversibility of these regressive processes, as shown by the analysis of molecular events at the site of injury and within ganglion cells. We review optic nerve repair from the perspective of the proximal axon stump being a major player in determining the successful formation of a growth cone. The axonal stump and consequently the prospective growth cone, communicates with astrocytes, microglial cells and the extracellular matrix via a panoply of molecular tools. We initially highlight these aspects on the basis of recent data from numerous laboratories. Then, we examine the mechanisms by which an injury-induced growth cone can sense its surroundings within the area distal to the injury. Based on requirements for successful axonal elongation within the optic nerve, we explore the models employed to instigate successful growth cone formation by ganglion cell stimulation and optic nerve remodelling, which in turn accelerate growth. Ultimately, with regard to the proteomics of regenerating retinal tissue, we discuss the discovery of isoforms of crystallins, with crystallin beta-b2 (crybb2) being clearly upregulated in the regenerating retina. Crystallins are produced and used to promote the elongation of growth cones. In vivo and in vitro, crystallins beta and gamma additionally promote the growth of axons by enhancing the production of ciliary neurotrophic factor (CNTF), indicating that they also act on astrocytes to promote axonal regrowth synergistically. These are the first data showing that axonal regeneration is related to crybb2 movement within neurons and to additional stimulation of CNTF. We demonstrate that neuronal crystallins constitute a novel class of neurite-promoting factors that probably operate through an autocrine and paracrine mechanism and that they can be used in neurodegenerative diseases. Thus, the post-injury fate of neurons cannot be seen merely as inevitable but, instead, must be regarded as a challenge to shape conditions for initiating growth cone formation to repair the damaged optic nerve.

Exercise and neuroprotection in an animal model of multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system resulting in accumulated loss of cognitive, sensory, and motor function.PURPOSETo evaluate the neuropathological effects of voluntary exercise in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.METHODSTwo groups of C57BL/6J mice were immunized with myelin oligodendrocyte glycoprotein (MOG) and then randomized to a cage with a running wheel or a locked wheel.RESULTSExercising EAE mice exhibited less severe neurological disease score (0.95 ± 0.97 exercise, 1.51 ± 0.85 sedentary), and later onset of disease when compared to sedentary EAE animals (14.83 ± 0.75 days, exercise, 12.67 ± 0.82 days, sedentary). Immune cell infiltration in the ventral white matter tracts of the lumbar spinal cord was reduced in the EAE exercise group by 47.5% when compared to sedentary EAE animals. Neurofilament immunolabeling in the anterior corticospinal tract displayed a more random distribution of axons and apparent loss of smaller diameter axons with a 44% greater loss of fluorescence immunolabeling in the sedentary EAE animals.CONCLUSIONOur findings provide evidence that voluntary exercise results in reduced and attenuated disability, reductions in autoimmune cell infiltration, and preservation of axons within the lumbar spinal cord of mice with EAE.

254 MODULATION OF THE URETHRAL CLOSURE REFLEX DURING SNEEZING BY SPINAL CHOLINERGIC PATHWAYS IN RATS

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2012254 MODULATION OF THE URETHRAL CLOSURE REFLEX DURING SNEEZING BY SPINAL CHOLINERGIC PATHWAYS IN RATS Satoru Yoshikawa and Naoki Yoshimura Satoru YoshikawaSatoru Yoshikawa Pittsburgh, PA More articles by this author and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.311AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stress urinary incontinence (SUI) is defined as involuntary leakage of urine under abdominal stress conditions such as sneezing. Previous studies reported that the urethral closure reflex (UCR) during sneezing is a crucial defense mechanism preventing urinary leakage, and that both noradrenergic and serotonergic pathways in the sacral spinal cord contribute to the UCR. However, a role of cholinergic pathways in the UCR has not been elucidated. We therefore investigated the effect of intrathecal (i.t.) administration of an acetylcholine (ACh) esterase inhibitor, which increases ACh in the synaptic terminal, and anti-cholinergic agents on the UCR in rats. METHODS In female SD rats, sneeze reflex was induced by their whisker cut and inserted into the nostril under urethane anesthesia. Urethral responses were measured using a mirotransducer-tipped catheter inserted into the middle urethra from the urethral orifice. An ACh esterase inhibitor (neostigmine: 0.1-3 nmol, i.t.) was administered at the level of L6-S1 spinal cord, and then the changes in amplitudes of urethral responses during sneezing (A-URS) and urethral basal pressure (UBP) were recorded. A muscarinic receptor blockers (atropine: 0.03-3 nmol) or a nicotinic receptor blocker (mecamylamine: 30 nmol) were also administered i.t. before the administration of neostigmine (3 nmol, i.t.). RESULTS Neostigmine dose-dependently and significantly decreased A-URS at all doses tested with approximately 70% reduction at 3 nmol (Fig. A). However, there was no change in UBP. (Fig. B). The neostigmine (3 nmol)-induced decrease in A-URS was dose-dependently reversed by atropine (non-selective antagonist) compared to the vehicle group(p<0.05) (Fig. C). Mecamylamine showed a tendency for suppression of neostigmine effects without statistical significance compared to the vehicle group. On the other hand, none of muscarinic or nicotinic blockers by themselves induced any significant changes in either A-URS or UBP. CONCLUSIONS These data indicate that an increase in endogenous ACh at the sacral spinal cord inhibits the UCR as shown by a decrease in A-URS during sneezing via activation of muscarinic receptors. These new findings may imply that enhancement of the spinal cholinergic function could be involved in the pathological mechanism inducing SUI. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e103 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satoru Yoshikawa Pittsburgh, PA More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of Spinal Cord Section on Inspiratory Pressure Generation During High Frequency Spinal Cord Stimulation (HF‐SCS)

ObjectiveHF‐SCS is a novel and more physiologic method of inspiratory muscle activation which involves activation of spinal cord pathways. The specific pathways by which inspiratory motoneurons are activated by this method however are unknown. The aim of the present study was to evaluate the potential role of upper cervical inspiratory neurons on the observed responses.MethodsIn 6 anesthetized and spinalized (C1 level) dogs, HF‐SCS was applied at T2 level. Airway pressure generation (P) was monitored as an index of the degree of inspiratory muscle activation before and following sequential spinal sections at the C4 (to eliminate upper cervical propriospinal neurons) and subsequently the C8 level.ResultsDuring HF‐SCS, P at FRC was 68±6 cmH2O. Sequential bilateral dorsal columns (DC), lateral funiculi (LF) and complete section (CS) at C4, resulted in no significant changes in P (69±5, 67±5 and 65±7 cmH2O respectively, NS). While DC section at C8 resulted in no changes in P (63±5 cmH2O), LF section resulted in significant reduction in P to 18±3 cmH2O (p&lt;0.05). Subsequent CS resulted in no further reduction in P (14±1 cmH2O, NS).ConclusionDuring upper thoracic HF‐SCS, activation of the phrenic motoneuron pools does not involve upper cervical propriospinal inputs. The phrenic motoneuron pools are activated via spinal pathways located bilaterally in the lateral funiculi.Support: NIH‐NINDS (R01NS064157).

Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI.

Changes in correlation between spontaneous activity of dorsal horn neurones lead to differential recruitment of inhibitory pathways in the cat spinal cord

Simultaneous recordings of cord dorsum potentials along the lumbo-sacral spinal cord of the anaesthetized cat revealed the occurrence of spontaneous synchronous negative (n) and negative-positive (np) cord dorsum potentials (CDPs). The npCDPs, unlike the nCDPs, appeared preferentially associated with spontaneous negative dorsal root potentials (DRPs) resulting from primary afferent depolarization. Spontaneous npCDPs recorded in preparations with intact neuroaxis or after spinalization often showed a higher correlation than the nCDPs recorded from the same pair of segments. The acute section of the sural and superficial peroneal nerves further increased the correlation between paired sets of npCDPs and reduced the correlation between the nCDPs recorded from the same pair of segments. It is concluded that the spontaneous nCDPs and npCDPs are produced by the activation of interconnected sets of dorsal horn neurones located in Rexed's laminae III–IV and bilaterally distributed along the lumbo-sacral spinal cord. Under conditions of low synchronization in the activity of this network of neurones there would be a preferential activation of the intermediate nucleus interneurones mediating Ib non-reciprocal postsynaptic inhibition. Increased synchronization in the spontaneous activity of this ensemble of dorsal horn neurones would recruit the interneurones mediating primary afferent depolarization and presynaptic inhibition and, at the same time, reduce the activation of pathways mediating Ib postsynaptic inhibition. Central control of the synchronization in the spontaneous activity of dorsal horn neurones and its modulation by cutaneous inputs is envisaged as an effective mechanism for the selection of alternative inhibitory pathways during the execution of specific motor or sensory tasks.

Fluoro-ruby retrograde tracing and three- dimensional visualization of the corticospinal tract in the guinea pig.

Fluoro-ruby was injected into the posterior funiculus of the spinal cord in the cervical (C5–T2) and lumbar (L3-6) segments of adult guinea pigs. The spinal cord was cut into serial frozen sections. The Fluoro-ruby labeling was clearly delineated from the surrounding structure. The labeling traversed the cervical, thoracic and lumbar segments, and was located on the ventral portion of the posterior funiculus on the injected side, proximal to the intermediate zone of the dorsal gray matter. The fluorescence area narrowed rostro-caudally. The spinal cord, spinal cord gray matter and corticospinal tract were reconstructed using 3D-DOCTOR 4.0 software, resulting in a robust three-dimensional profile. Using functionality provided by the reconstruction software, free multi-angle observation and sectioning could be conducted on the spinal cord and corticospinal tract. Our experimental findings indicate that the Fluoro-ruby retrograde fluorescent tracing technique can accurately display the anatomical location of corticospinal tract in the guinea pig and that three-dimensional reconstruction software can be used to provide a three-dimensional image of the corticospinal tract.

Potential long-term benefits of acute hypothermia after spinal cord injury

Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury, the primary focus has been assessing the effects of hypothermia on behavioral and histologic outcomes. Although a few studies have investigated electrophysiological changes in descending motor pathways with motor-evoked potentials recorded during cooling, we report here hypothermia induced increased electrical conduction in the ascending spinal cord pathways with somatosensory-evoked potentials in injured rats. In our experiments, these effects lasted long after the acute hypothermia and were accompanied by potential long-term improvements in motor movement. Laboratory investigation. University medical school. Twenty-one female Lewis rats. Hypothermia. All animals underwent spinal cord contusion with the NYU-Impactor by a 12.5-mm weight drop at thoracic vertebra T8. A group (n = 10) was randomly assigned for a systemic 2-hr hypothermia episode (32 ± 0.5°C) initiated approximately 2.0 hrs postinjury. Eleven rats were controls with postinjury temperature maintained at 37 ± 0.5°C for 2 hrs. The two groups underwent preinjury, weekly postinjury (up to 4 wks) somatosensory-evoked potential recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histologic analysis at postinjury day 3 and day 28. Compared with controls, the hypothermia group showed significantly higher postinjury somatosensory-evoked potential amplitudes with longer latencies. The BBB scores were also higher immediately after injury and 4 wks later in the hypothermia group. Importantly, specific changes in the Basso, Beattie, Bresnahan scores in the hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histologic evaluations showed more tissue preservation in the hypothermia group. After spinal cord injury, early systemic hypothermia provided significant neuroprotection weeks after injury through improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and postacute periods after injury.

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA

LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the cerebral white matter and specific brain stem and spinal cord tracts. LBSL is caused by mutations in the gene DARS2, which encodes mtAspRS (mitochondrial aspartyl-tRNA synthetase). The selective involvement of specific white matter tracts in LBSL is striking since this protein is ubiquitously expressed. Almost all LBSL patients have one mutation in intron 2 of DARS2, affecting the splicing of the third exon. Using a splicing reporter construct, we find cell-type-specific differences in the sensitivity to these mutations: the mutations have a larger effect on exon 3 exclusion in neural cell lines, especially neuronal cell lines, than in non-neural cell lines. Furthermore, correct inclusion of exon 3 in the normal mtAspRS mRNA occurs less efficiently in neural cells than in other cell types, and this effect is again most pronounced in neuronal cells. The combined result of these two effects may explain the selective vulnerability of specific white matter tracts in LBSL patients.

Can motor volition be extracted from the spinal cord?

BackgroundSpinal cord injury (SCI) results in the partial or complete loss of movement and sensation below the level of injury. In individuals with cervical level SCI, there is a great need for voluntary command generation for environmental control, self-mobility, or computer access to improve their independence and quality of life. Brain-computer interfacing is one way of generating these voluntary command signals. As an alternative, this study investigates the feasibility of utilizing descending signals in the dorsolateral spinal cord tracts above the point of injury as a means of generating volitional motor control signals.MethodsIn this work, adult male rats were implanted with a 15-channel microelectrode array (MEA) in the dorsolateral funiculus of the cervical spinal cord to record multi-unit activity from the descending pathways while the animals performed a reach-to-grasp task. Mean signal amplitudes and signal-to-noise ratios during the behavior was monitored and quantified for recording periods up to 3 months post-implant. One-way analysis of variance (ANOVA) and Tukey’s post-hoc analysis was used to investigate signal amplitude stability during the study period. Multiple linear regression was employed to reconstruct the forelimb kinematics, i.e. the hand position, elbow angle, and hand velocity from the spinal cord signals.ResultsThe percentage of electrodes with stable signal amplitudes (p-value < 0.05) were 50% in R1, 100% in R2, 72% in R3, and 85% in R4. Forelimb kinematics was reconstructed with correlations of R2 > 0.7 using tap-delayed principal components of the spinal cord signals.ConclusionsThis study demonstrated that chronic recordings up to 3-months can be made from the descending tracts of the rat spinal cord with relatively small changes in signal characteristics over time and that the forelimb kinematics can be reconstructed with the recorded signals. Multi-unit recording technique may prove to be a viable alternative to single neuron recording methods for reading the information encoded by neuronal populations in the spinal cord.

Effects of Hematopoietic Autologous Stem Cell Transplantation to the Chronically Injured Human Spinal Cord Evaluated by Motor and Somatosensory Evoked Potentials Methods

International standards for stem cell treatment of neurological disorders have not yet been established. In particular, specific quantitative methods have not yet been adopted to assess the effectiveness of stem cell treatment. The aim of this study is to evaluate the functional changes detectable by conventional neurophysiologic methods in an injured spinal cord during stem cell therapy. Twenty adult patients with chronic spinal cord injury at C4-C8 level were examined by somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) methods, the first time prior to the treatment and then regularly during its course (1-4 years). The treatment consisted of repeated intrathecal transplantations of autologous hematopoietic stem cells. After at least 1 year of treatment, four effects were detected: 1) restoration of the initially absent short-latency SEP (three patients); 2. N20P23 interpeak amplitude increase in SEP elicited by median nerve stimulation (four patients); 3) P38 latency reduction in SEP elicited by tibial nerve stimulation (two patients); 4) appearance of MEP (three patients). The nonidentical effects of stem cell transplantation in different patients presumably reflect the variety of the regeneration processes in different pathways of the spinal cord, depending on the extent and nature of lesion of the spinal cord pathways in different patients. The local effects of stem cell treatment at the cervical level were evaluated by median SEP and wrist muscle MEP demonstrate the ability of stem cells to spread within the spinal cord at least from lumbar to the cervical level, home there, and participate in the neurorestoration processes.

Multiple drug delivery hydrogel system for spinal cord injury repair strategies

The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug delivery systems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drug delivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion.

Cerebral hemispherectomy: Sensory scores before and after intensive mobility training

Purpose: It is unclear whether sensory modalities can be modified by rehabilitation and if sensory functions vary on the affected side many years after cerebral hemispherectomy. This pilot, proof-of-concept study assessed light touch and proprioception before and after 10days of intensive mobility training in individuals after hemispherectomy. Methods: Light touch and proprioception of the upper and lower extremity was measured using the Fugl-Meyer sensory subtest on the paretic side in 18 individuals with hemispherectomy before and after mobility training. Sensory scores and differences related to mobility training were compared with clinical variables. Results: Patients were 7.1±5.7years from time of surgery to sensory assessment and mobility training. Light touch scores were 81±22% and proprioception values were 64±23% of normal (p=0.0022). Light touch did not correlate with proprioception scores, and differences comparing after with before mobility training did not correlate. In multivariate analysis, younger age at seizure onset correlated with better light touch scores, and older age at onset correlated with improvements in light touch scores with mobility training. By comparison, proprioception scores were better in individuals with perinatal infarcts compared with Rasmussen encephalitis and Sturge-Weber. Post-training, proprioception scores were better in Sturge-Weber cases. Conclusion: Light touch was less affected than proprioception on the paretic side after cerebral hemispherectomy. Improvements with mobility training correlated with older age at seizure onset and etiology. These findings suggest that many years after epilepsy surgery sensory functions are not static supporting the notion of existing developmental neuroplasticity of the remaining cerebral cortex along with brain stem and spinal cord pathways.

Poster 160 Biofeedback Therapy in Neurogenic Bladder Dysfunction

The micturition response is a complex mechanism involving the frontal lobe of the brain, the pons, spinal cord pathways, sacral spinal cord, and the peripheral nervous system. Injury to any of the components involved in this complex interplay of neurologic pathways can have neurogenic bladder dysfunction resulting in urinary retention, overactivity and urinary incontinence, or a mixed dysfunction. Usually, there is difficulty in fully voiding urine. Incontinence then occurs in the form of overflow.

Orientation entropy analysis of diffusion tensor in healthy and myelopathic spinal cord

The majority of nerve fibers in the spinal cord run longitudinally, playing an important role in connecting the brain to the peripheral nerves. There is a growing interest in applying diffusion tensor imaging (DTI) to the evaluation of spinal cord microarchitecture. The current study sought to compare the organization of longitudinal nerve fibers between healthy and myelopathic spinal cords using entropy-based analysis of principal eigenvector mapping. A total of 22 subjects were recruited, including 14 healthy subjects, seven cervical myelopathy (CM) patients with single-level compression, and one patient suffering from multi-level compression. Diffusion tensor magnetic resonance (MR) images of the cervical spinal cord were obtained using a pulsed gradient, spin-echo echo-planar imaging (SE-EPI) sequence with a 3T MR system. Regions of interest (ROIs) were drawn manually to cover the spinal cord, and Shannon entropy was calculated in principal eigenvector maps. The results revealed no significant differences in orientation entropy values along the whole length of cervical spinal cord in healthy subjects (C2-3: 0.73±0.05; C3-4: 0.71±0.07; C4-5: 0.72±0.048; C5-6: 0.71±0.07; C6-7: 0.72±0.07). In contrast, orientation entropy values in myelopathic cord were significantly higher at the compression site (0.91±0.03), and the adjacent levels (above: 0.85±0.03; below: 0.83±0.05). This study provides a novel approach to analyze the orientation information in diffusion MR images of healthy and diseased spinal cord. These results indicate that orientation entropy can be applied to determine the contribution of each compression level to the overall disorganization of principal nerve tracts of myelopathic spinal cord in cases with multi-level compression.

Effect of intercompartmental water exchange on the apparent myelin water fraction in multiexponential T2 measurements of rat spinal cord

The myelin water fraction has been used as a quantitative measure of the amount of myelin present in tissue. However, recent work has suggested that intercompartmental exchange of water between myelin and nonmyelin compartments may cause the myelin water fraction to underestimate the true myelin content of tissue. In this work, multiexponential T(2) experiments were performed in vivo within the rat spinal cord, and a wide variation of the myelin water fraction (10-35%) was measured within four rat spinal cord tracts with similar myelin content. A numerical simulation based upon segmented histology images was used to quantitatively account for T(2) variations between tracts. The model predicts that a difference in exchange between the four spinal cord tracts, mediated by a difference in the average axon radius and myelin thickness, is sufficient to account for the variation in myelin water fraction measured in vivo.

A diffusion gradient optimization framework for spinal cord diffusion tensor imaging

The uncertainty in the estimation of diffusion model parameters in diffusion tensor imaging (DTI) can be reduced by optimally selecting the diffusion gradient directions utilizing some prior structural information. This is beneficial for spinal cord DTI, where the magnetic resonance images have low signal-to-noise ratio and thus high uncertainty in diffusion model parameter estimation. Presented is a gradient optimization scheme based on D-optimality, which reduces the overall estimation uncertainty by minimizing the Rician Cramer-Rao lower bound of the variance of the model parameter estimates. The tensor-based diffusion model for DTI is simplified to a four-parameter axisymmetric DTI model where diffusion transverse to the principal eigenvector of the tensor is assumed isotropic. Through simulations and experimental validation, we demonstrate that an optimized gradient scheme based on D-optimality is able to reduce the overall uncertainty in the estimation of diffusion model parameters for the cervical spinal cord and brain stem white matter tracts.

FK506 promotes repair of injured spinal cord pathway after neural stem cell transplantation

Objective To observe the effect of tacrolimus(FK506)in promoting repair of the injured spinal cord pathway after neural stem cell transplantation in rats. Methods A neurysm clip was used to compress the T8 spinal cord segment of SD rats under microscope to establish model of spinal cord injury.The rats were randomly divided into three groups seven days after injury,ie,control group (injection of normal saline at the injury center),transplantation group(injection of neural stem cells,NSCs,at the injury center),FK506 group(injection of NSCs at the injury center plus 7 days of intrapernerve conduction was compared by using the Basso-Beatfle-Bresnahan (BBB) scale,BDA tracing,somatosensory evoked potential(SEP)and motor evoked potentials(MEP)monitoring at 1,2,4 and 8weeks. Results The motor function of the hind limb after injury was recovered in various degrees with time,with the most significant recovery at 4 weeks.The BBB score reached 6,the maximum at 8 weeks.BDA tracing showed that some nerve fibers were found crossing the injured center of the spinal cord one week later in FK506 group and cell transplantation group,that BDA-positive labeled corticospinal tract fibets were seen across the injury site in all groups by the end ofthe eight weeks.In the FKS06 group,the regeneration could be observed even as 1.7 cm away from tlle injury center.SEP latency was significantly shorter in the FK506 group after two weeks(P<0.05)and the MEP latency in the FK506 group was shortened significantly at four weeks compared with the other groups(P<0.05),indicating that the immunosuppressants could promote the recovery of the injured spihal cord,shorten the latency of SEP and MEP，improve SEP at early stage and MEP at late stage．Conclusions Systemic application immunosuppressive agents FK506 plays an important role in neuroprotection and neurotrophy，which promotes the repair of the injured spinal cord after neural stem cell transplantation． Key words: Spinal cord injuries; FK506; Stem cell transplantation; Evoked potentials