Ventral Funiculus Research Articles

CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well as Oligodendrocytes during Repair of CNS Demyelination

After central nervous system (CNS) demyelination-such as occurs during multiple sclerosis-there is often spontaneous regeneration of myelin sheaths, mainly by oligodendrocytes but also by Schwann cells. The origins of the remyelinating cells have not previously been established. We have used Cre-lox fate mapping in transgenic mice to show that PDGFRA/NG2-expressing glia, a distributed population of stem/progenitor cells in the adult CNS, produce the remyelinating oligodendrocytes and almost all of the Schwann cells in chemically induced demyelinated lesions. In contrast, the great majority of reactive astrocytes in the vicinity of the lesions are derived from preexisting FGFR3-expressing cells, likely to be astrocytes. These data resolve a long-running debate about the origins of the main players in CNS remyelination and reveal a surprising capacity of CNS precursors to generate Schwann cells, which normally develop from the embryonic neural crest and are restricted to the peripheral nervous system.

Effects of different loading conditions on the stress features of hyperextension injury to the cervical spinal cord

Objective To investigate the mechanical responses by the cervical spinal cord to the hyperextension injury under different loading conditions. Methods A three dimensional finite element model of the cervical spinal cord was built and imported into the preprocessor of the Ansys software for assigning boundary and different loading conditions. Then the extension and pinching conditions were simulated after the solution module was entered. The stress results of 9 different anatomical regions in the cross-section of the cervical spinal cord were read and analyzed in the postprocessor of the Ansys software. Results The localized stress mainly occurred at the anterior horn and posterior horn in the gray matter, the anterior funiculus, the medial part of the lateral funiculus, and the lateral part of the posterior funiculus, with the average magnitude decreasing successively. The magnitude of the stress increased with the severity of the cervical spine injury. The maximum stress increment occurrred at the anterior horn. Significant differences in the stress increment were observed between the anterior horn and the lateral funiculus( P 0. 05). Conclusions The cervical hyperextension injury mainly leads to injury to the motor neuron of the anterior horn. More damage to the motor neuron dominating the intrinsic muscle of hand can lead to poorer prognosis. A greater injury load may cause stress to distribute onto more adjacent white matter. Key words: Spinal cord injuries; Finite element analysis; Biomechanics

Human cervical spinal cord funiculi: Investigation with magnetic resonance diffusion tensor imaging

To use spinal cord diffusion tensor imaging (DTI) for investigating human cervical funiculi, acquire axial diffusion magnetic resonance imaging (MRI) data with an in-plane resolution sufficient to delineate subquadrants within the spinal cord, obtain corresponding DTI metrics, and assess potential regional differences. Healthy volunteers were studied with a 3 T Siemens Trio MRI scanner. DTI data were acquired using a single-shot spin echo EPI sequence. The spatial resolution allowed for the delineation of regions of interest (ROIs) in the ventral, dorsal, and lateral spinal cord funiculi. ROI-based and tractography-based analyses were performed. Significant fractional anisotropy (FA) differences were found between ROIs in the dorsal and ventral funiculi (P = 0.0001), dorsal and lateral funiculi (P = 0.015), and lateral and ventral funiculi (P = 0.0002). Transverse diffusivity was significantly different between ROIs in the ventral and dorsal funiculi (P = 0.003) and the ventral and lateral funiculi (P = 0.004). Tractography-based quantifications revealed DTI parameter regional differences that were generally consistent with the ROI-based analysis. Original contributions are: 1) the use of a tractography-based method to quantify DTI metrics in the human cervical spinal cord, and 2) reported DTI values in various funiculi at 3 T.

Activity of 2′, 3′-Cyclic Nucleotide 3′-Phosphodiesterase (CNPase) in Spinal Cord with Spongy Change Induced by a Single Oral Dose of Aniline in Rats

A spongy change in the spinal cord white matter was observed in four-week-old rats treated with aniline. Although this change was found to be a result of the myelin sheath splitting at the ultrastructural level, the mechanism is unknown. This study was conducted to identify the mechanism of the spongy change in aniline-treated rats. The spongy change in the spinal cord white matter was first detected on day 5 in the histopathologic examination. The incidence and severity of the lesions, especially in the lateral and ventral funiculi of the thoracic spinal cord white matter, increased prominently from day 8 to day 10. In all rats, immunohistochemical staining by anti-2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) occurred along the cytoplasmic boundaries of the normal oligodendroglia. However, mild to moderate anti-CNPase staining extended to the swollen cytoplasm of the oligodendroglia in the aniline-treated rats from day 2 to day 4. In the electron microscopic examination, free ribosomes and rough endoplasmic reticula in the cytoplasm of the oligodendroglia increased on days 3 and 4. These changes were considered to be related to CNPase expression. However, CNPase expression decreased, whereas the spongy changes were detected from day 5. The reduction in CNPase expression may contribute to the changes in the myelin morphology observed in aniline intoxication.

Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers.

BackgroundIt has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF) may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i) how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii) if a response is related to BDNF protein level and distribution.We investigated the effect of training in rats spinalized at low thoracic segments on the level and distribution of BDNF immunoreactivity (IR) in ventral quadrants of the lumbar segments, in conjunction with markers of presynaptic terminals, synaptophysin and synaptic zinc.ResultsTraining improved hindlimb stepping in spinal animals evaluated with modified Basso-Beattie-Bresnahan scale. Grades of spinal trained animals ranged between 5 and 11, whereas those of spinal were between 2 and 4. Functional improvement was associated with changes in presynaptic markers and BDNF distribution. Six weeks after transection, synaptophysin IR was reduced by 18% around the large neurons of lamina IX and training elevated its expression by over 30%. The level of synaptic zinc staining in the ventral horn was unaltered, whereas in ventral funiculi it was decreased by 26% postlesion and tended to normalize after the training. Overall BDNF IR levels in the ventral horn, which were higher by 22% postlesion, were unchanged after the training. However, training modified distribution of BDNF in the processes with its predominance in the longer and thicker ones. It also caused selective up-regulation of BDNF in two classes of cells (soma ranging between 100-400 μm2 and over 1000 μm2) of the ventrolateral and laterodorsal motor nuclei.ConclusionOur results show that it is not BDNF deficit that determines lack of functional improvement in spinal animals. They indicate selectivity of up-regulation of BDNF in distinct subpopulations of cells in the motor nuclei which leads to changes of innervation targeting motoneurons, tuned up by locomotor activity as indicated by a region-specific increase of presynaptic markers.

Localization of an axon growth inhibitory molecule Nogo and its receptor in the spinal cord of mouse embryos

The localization of an axon growth inhibitory molecule Nogo and its receptor (NgR) was investigated in the mouse spinal cord during prenatal development of the commissural pathway. Using the antibody N18, an intense signal for Nogo was localized largely on radial glia processes that are immunoreactive to RC2 antibody during the major period of commissural axon growth and was gradually reduced towards the end of gestation. The glial processes ramified extensively in the ventral funiculus and resided within the interfascicular space between the longitudinally projecting axons. Axonal localization of Nogo was observed on the premidline segment of commissural axons and on axons in the dorsal and ventral funiculi, but only at the earliest stage of pathway development. Nogo signals were initially weak on the glial processes during the period of axon crossing in the floor plate but was elevated when the decussation is finished. NgR was expressed on the commissural axons; the expression pattern is spatially regulated, being low in the premidline and midline courses but is upregulated when the axons leave the floor plate. These expression patterns raise the possibilities that the glial-specific form of Nogo may be involved in the guidance of commissural axons by (i) preventing recrossing of axons across the midline through an upregulation of axonal NgR and (ii) partitioning axons in the ventral funiculus into longitudinal fascicles.

Preliminary study of cervical spinal cord in patients with amyotrophic lateral sclerosis using MR diffusion tensor imaging

Objective To determine whether normal-appearing cervical spinal cord in patients with amyotrophic lateral sclerosis (ALS) has abnormal changes based on the quantitative measurement in healthy volunteers. Methods Conventional MRI and axial DTI were obtained in 16 patients with ALS (ALS group) and 16 age-matched control subjects (normal group) . ADC, fractional anisotropy (FA) and relative anisotropy(RA)imagcs were obtained on workstation (AW4. 2). ROIs (5 mm × 5 mm) were placed in anterior funicalus, posterior funiculus, and bilateral lateral corticospinal tracts (LCTs), respectively, at the same slice (C3). Independent-sample t test was used for comparison of parameters between the two groups. Correlations between DTI parameters of ALS and ALS course, Norris score, and ALSFRS were carried out separately by Pearson correlation analysis. Results FA and RA values of bilateral LCTs were decreased significantly. FA/RA values of left LCT were 0.762±0.089 and 0.762±0.107 in ALS group, while they were 0.863±0.098 and 0.890±0.105 in control group, respectively. FA/RA values of right LCT were 0.751±0.065 and 0.772±0.082 in ALS group, and they were 0.843±0.118 and 0.863±0.134 in control group, respectively, they were decreased significantly (t = 2.575、4.195、2.246、2.218, P 0.05) between ADC values of left and right CSTs in ALS group [(0.744±0.162) × 10-3, (0.767±0.141) × 10-3 mm2/s] and control group [(0.640±0.149) ×10-3, (0.643±0.168) ×10-3 mm2/s)]. FA, RA and ADC values of ALS patients in anterior funiculus were 0.637±0.113, 0.622±0.138, (0.950±0.354)×10-3 mm2/s, in control group they were 0.670±0.117, 0.656±0.136, (0.865±0.238) × 10-3 mm2/s, there were no significant differences (t = 0.854, - 0.704, - 1.155,P > 0.05). FA, RA and ADC values of ALS patients in posterior funieulus were 0.886±0.073, 0.920±0.100, (0.613±0.137)×10-3 mm2/s, in control group they were 0.906±0.078, 0.914±0.135, (0.636±0.224) × 10-3 mm2/s, there were no significant differences (t = 1.655, - 0.148, - 1.360; P > 0.05). No significant correlation existed between FA and RA values and disease course, Norris and ALSFRS score (P > 0.05), in left and right LCTs. Conclusion DTI with SE-EPI technique is simple and sensitive to detect the pathological changes of the cervical spinal cord in ALS patients. DTI can reveal the abnormalities which are normal appearing on conventional T2WI. Key words: Amyotrophic lateral sclerosis; Diffusion magnetic resonance imaging; Spinal cord

Encephalomyelopathy and Polyneuropathy Associated with Neuronal Vacuolation in Two Boxer Littermates

Neuronal vacuolation and spinocerebellar degeneration is a rare, presumably inherited condition that is reported only in Rottweilers and in crossbred dogs with known or potential Rottweiler heritage. Gross and histopathologic findings include laryngeal muscle atrophy, neuronal vacuolation, and a combined central and peripheral axonopathy. Two 6-month-old Boxer puppies from the same litter were referred for evaluation of progressive pelvic limb paresis and ataxia, upper airway stridor, and visual deficits. Examination of each dog suggested a combined myelopathy and peripheral neuropathy, as well as congenital ocular disease. Gross lesions were limited to atrophy of the intrinsic laryngeal muscles. Histopathologically, there was diffuse loss of axons and myelin in the dorsolateral and ventral funiculi throughout the spinal cord and extending into the caudal aspect of the brain stem. Vacuolation of scattered neuronal cell bodies was present in the spinal cord and selected brain stem nuclei. Multifocal axonal degeneration and demyelination was observed in the recurrent laryngeal nerve, sciatic nerve, and brachial plexus and was most severe in the recurrent laryngeal nerve. Ocular abnormalities included microphthalmia, cataracts, and retinal dysplasia. The findings in these Boxer dogs, unrelated to the Rottweiler breed, are analogous to the syndrome of neuronal vacuolation and spinocerebellar degeneration reported in Rottweilers.

Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE), an induced model of Multiple Sclerosis presents spinal cord demyelination, axonal pathology and neuronal dysfunction. Previous work has shown that progesterone attenuated the clinical severity, demyelination and neuronal dysfunction of EAE mice (Garay et al., J. Steroid Biochem. Mol. Biol., 2008). Here we studied if progesterone also prevented axonal damage, a main cause of neurological disability. To this end, some axonal parameters were compared in EAE mice pretreated with progesterone a week before immunization with MOG 40–54 and in a group of steroid-free EAE mice. On day 16th after EAE induction, we determined in both groups and in control mice: a) axonal density in semithin sections of the spinal cord ventral funiculus; b) appearance of amyloid precursor protein (APP) immunopositive spheroids as an index of damaged axons; c) levels of the growth associated protein GAP43 mRNA and immunopositive cell bodies, as an index of aberrant axonal sprouting. Steroid-naive EAE mice showed decreased axonal density, shrunken axons, abundance of irregular vesicular structures, degenerating APP+ axons, increased expression of GAP43 mRNA and immunoreactive protein in motoneurons. Instead, EAE mice receiving progesterone treatment showed increased axonal counts, high proportion of small diameter axons, reduced APP+ profiles, and decreased GAP43 expression. In conclusion, progesterone enhanced axonal density, decreased axonal damage and prevented GAP43 hyperexpression in the spinal cord of EAE mice. Thus, progesterone also exerts protective effects on the axonal pathology developing in EAE mice.

The periaqueductal grey modulates sensory input to the cerebellum: a role in coping behaviour?

The paths that link the periaqueductal grey (PAG) to hindbrain motor circuits underlying changes in behavioural responsiveness to external stimuli are unknown. A major candidate structure for mediating these effects is the cerebellum. The present experiments test this directly by monitoring changes in size of cerebellar responses evoked by peripheral stimuli following activation of the PAG. In 22 anaesthetized adult Wistar rats, climbing fibre field potentials were recorded from the C1 zone in the paramedian lobule and the copula pyramidis of the cerebellar cortex evoked, respectively, by electrical stimulation of the ipsilateral fore- and hindlimb. An initial and a late response were attributable to activation of Abeta and Adelta peripheral afferents respectively (hindlimb onset latencies 16.9 and 23.8 ms). Chemical stimulation at physiologically-identified sites in the ventrolateral PAG (a region known to be associated with hyporeactive immobility) resulted in a significant reduction in size of both the Abeta and Adelta evoked field potentials (mean reduction relative to control +/- SEM, 59 +/- 7.5 and 66 +/- 11.9% respectively). Responses evoked by electrical stimulation of the dorsal or ventral funiculus of the spinal cord were also reduced by PAG stimulation, suggesting that part of the modulation may occur at supraspinal sites (including at the level of the inferior olive). Overall, the results provide novel evidence of descending control into motor control centres, and provide the basis for future studies into the role of the PAG in regulating motor activity in different behavioural states and in chronic pain.

Three-Dimensional Finite Element Model of the Cervical Spinal Cord

A three-dimensional finite element investigation. To create a three-dimensional finite element model of the cervical spinal cord enlargement and to simulate a hyperextension injury of the cervical cord. Experimental studies are difficult to simulate the complex mechanism of spinal cord injuries. The introduction of three-dimensional modeling technique into neurotrauma studies is essential to further understand mechanical behavior of the nerve tissue during traumatic injuries. Geometrical reconstruction of cervical spinal cord enlargement was developed based on the morphologic features of each segment of the fresh human cervical cord. After the validation of the model, the pinching condition in the hyperextension injuries was simulated with compressive and extension forces applied on the cervical enlargement model. The average von Mises stress of the 9 anatomic regions, such as anterior funiculus, lateral part of the lateral funiculus, medial part of the lateral funiculus, lateral part of the posterior funiculus, medial part of the posterior funiculus, anterior horn, the bottom of anterior horn, the apex of posterior horn, the cervix cornu posterioris, and caput cornu posterioris was recorded. The force-displacement response of the spinal cord under compression and axial tension loading was close to the experimental results reported in the literature. The stress distribution of the spinal cord according to the numerical simulation and the morphologic features of the in vivo experiment were also in close agreement. Hyperextension injury simulation showed high localized stress at the anterior and posterior horn in the gray matter. The finite element method as a three-dimensional modeling technique can improve the understanding of the biomechanical behavior of the spinal cord. The results of hyperextension injury simulation of the cervical spinal cord probably account for the predominance of the hand weakness in patients with central cord injury.

Degenerative Myelopathy in Two Boxer Dogs

Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs.

Degenerative Myelopathy in 18 Pembroke Welsh Corgi Dogs

Postmortem examination was performed on 18 Pembroke Welsh Corgi dogs (mean age 12.7 years) with clinical signs and antemortem diagnostic tests compatible with a diagnosis of degenerative myelopathy. Tissue sections from specific spinal cord and brain regions were systematically evaluated in all dogs. Axonal degeneration and loss were graded according to severity and subsequently compared across different spinal cord segments and funiculi. White matter lesions were identified in defined regions of the dorsal, lateral, and ventral funiculi. The dorsolateral portion of the lateral funiculus was the most severely affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits, with the exception of areas of mild astrogliosis in gray matter of the caudal medulla. Dogs with more severe lesions showed significant progression of axonal degeneration and loss at T12 and at cord segments cranial and caudal to T12. Severity of axonal loss in individual dogs positively correlated with the duration of clinical signs. The distribution of axonal degeneration resembled that reported in German Shepherd Dog degenerative myelopathy but differed with respect to the transverse and longitudinal extent of the lesions within more clearly defined funicular areas. Although these lesion differences might reflect disease longevity, they could also indicate a form of degenerative myelopathy unique to the Pembroke Welsh Corgi dog.

Imaging synaptically mediated responses produced by brainstem inputs onto identified spinal neurons in the neonatal mouse

Descending inputs to spinal cord neurons in mammals have previously been characterized functionally using microelectrode recording of single neurons, a technique with high spatial and temporal resolution but low yield. Consequently our knowledge about the functional connections between the brain and the spinal cord has been accumulating at a very low pace. Here we describe a high throughput optical recording approach in an ex vivo brainstem–spinal cord preparation of the neonatal mouse that permits screening many spinal neurons simultaneously for synaptic inputs from descending axons. The fluorescent calcium indicator calcium green dextran amine was loaded retrogradely into specific spinal neuron populations, including motoneurons (MNs) of the medial and lateral motor columns and two populations of interneurons with descending axons (dINs) in the ventral funiculus. Focal electrical stimulation of brainstem neuron populations with descending axons generated synaptic responses revealed by transient increases in intracellular calcium concentration in all four populations of spinal neurons. The resultant fluorescence signals could be readily visualized in individual MNs directly through the ventral white matter. In the more deeply located dINs, responses could be readily visualized in individual neurons from the surface of an oblique cut through the spinal cord. The rapid optical investigation of functional connections between brainstem descending neurons and various populations of spinal neurons in the living mammalian preparation should help uncover some of the key features of supraspinal sensory and motor control and provide a valuable tool for examining the re-innervation of spinal neurons by descending axons after spinal cord regeneration.

Degenerative Myelopathy in 18 Pembroke Welsh Corgi Dogs

Postmortem examination was performed on 18 Pembroke Welsh Corgi dogs (mean age 12.7 years) with clinical signs and antemortem diagnostic tests compatible with a diagnosis of degenerative myelopathy. Tissue sections from specific spinal cord and brain regions were systematically evaluated in all dogs. Axonal degeneration and loss were graded according to severity and subsequently compared across different spinal cord segments and funiculi. White matter lesions were identified in defined regions of the dorsal, lateral, and ventral funiculi. The dorsolateral portion of the lateral funiculus was the most severely affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits, with the exception of areas of mild astrogliosis in gray matter of the caudal medulla. Dogs with more severe lesions showed significant progression of axonal degeneration and loss at T12 and at cord segments cranial and caudal to T12. Severity of axonal loss in individual dogs positively correlated with the duration of clinical signs. The distribution of axonal degeneration resembled that reported in German Shepherd Dog degenerative myelopathy but differed with respect to the transverse and longitudinal extent of the lesions within more clearly defined funicular areas. Although these lesion differences might reflect disease longevity, they could also indicate a form of degenerative myelopathy unique to the Pembroke Welsh Corgi dog.

Recovery of overground locomotion following partial spinal lesions of different extent in the rat

In six rats with incomplete low thoracic spinal cord lesions of different extent, basic gait indices such as locomotor speed, step cycle duration, soleus (Sol) muscle activity duration, the interval between the onsets of Sol and tibialis anterior (TA) muscle activities and interlimb coordination were investigated by EMG analysis of the Sol and TA muscles recorded using chronic electrodes. The operated animals were divided into two subgroups: (1) those with a smaller lesion involving the dorsal quadrants of the spinal cord and, to a variable extent, the ventrolateral funiculi, and (2) those with an extensive lesion sparing only parts of the ventral funiculi. The locomotion of all rats was tested once a week for the first 5 weeks postsurgery and then once or twice a month, up to 3.5 months. The surgical lesions affected all analyzed gait indices: the locomotor speed decreased, while all other indices increased compared to recordings made preoperatively. In both subgroups the major improvement in locomotion occurred within the first 5 weeks following surgery and the rats reached a plateau in their recovery at around 2 months postoperatively. The late effects of injury depended on the severity of the spinal lesion: in the subgroup of rats with a smaller lesion, the postoperative changes in the different indices amounted to approximately 20%, while in the subgroup with extensive lesions this was increased by 20–50%, with changes in various indices being strongly correlated with the extent of the injury in individual animals. These postoperative changes were partly due to alterations in the relationships between the analyzed variables.

A Molecular Program for Contralateral Trajectory: Rig-1 Control by LIM Homeodomain Transcription Factors

Despite increasing evidence for transcriptional control of neural connectivity, how transcription factors regulate discrete steps in axon guidance remains obscure. Projection neurons in the dorsal spinal cord relay sensory signals to higher brain centers. Some projection neurons send their axons ipsilaterally, whereas others, commissural neurons, send axons contralaterally. We show that two closely related LIM homeodomain proteins, Lhx2 and Lhx9, are expressed by a set of commissural relay neurons (dI1c neurons) and are required for the dI1c axon projection. Midline crossing by dI1c axons is lost in Lhx2/9 double mutants, a defect that results from loss of expression of Rig-1 from dI1c axons. Lhx2 binds to a conserved motif in the Rig-1 gene, suggesting that Lhx2/9 regulate directly the expression of Rig-1. Our findings reveal a link between the transcriptional programs that define neuronal subtype identity and the expression of receptors that guide distinctive aspects of their trajectory.

In vivo diffusion tensor imaging of the rat spinal cord at 9.4T

To determine differences in diffusion measurements in white matter (WM) and gray matter (GM) regions of the rat cervical, thoracic, and cauda equina spinal cord using in vivo diffusion tensor imaging (DTI) with a 9.4T MR scanner. DTI was performed on seven rats in three slices at the cervical, thoracic, and cauda equina regions of the spinal cord using a 9.4T magnet. Axial diffusion weighted images (DWIs) were collected at a b-value of 1000 seconds/mm(2) in six directions. Regions of interest were identified via T2-weighted images for the lateral, dorsal, and ventral funiculi, along with GM regions. Analysis of variance (ANOVA) results indicated significant differences between every WM funiculus compared to GM for longitudinal apparent diffusion coefficient (lADC), transverse apparent diffusion coefficient (tADC), fractional anisotropy (FA), measured longitudinal anisotropy (MA1), and anisotropy index (AI). A significant difference in mean diffusivity (MD) between regions of the spinal cord was not found. Diffusion measurements were significantly different at each spinal level. In general, GM regions were significantly different than WM regions; however, there were few significant differences between individual WM regions. In vivo DTI of the rat spinal cord at 9.4T appears sensitive to the architecture of neural structures in the rat spinal cord and may be a useful tool in studying trauma and pathologies in the spinal cord.

Pyridoxine induced neuropathy by subcutaneous administration in dogs

To construct a sensory neuropathy model, excess pyridoxine (150 mg/kg s.i.d.) was injected subcutaneously in dogs over a period of 7 days. During the administrations period, the dogs experienced body weight reduction and proprioceptive loss involving the hindquarters. After pyridoxine administration was completed, electrophysiological recordings showed that the M wave remained at a normal state, but the H-reflex of the treated dogs disappeared at 7 days. The dorsal funiculus of L4 was disrupted irregularly in the axons and myelin with vacuolation. The dorsal root ganglia of L4, and sciatic and tibial nerves showed degenerative changes and vacuolation. However, the lateral and ventral funiculi of L4 showed a normal histopathologic pattern. Although this subcutaneous administration method did not cause systemic toxicity and effectively induced sensory neuropathy, this study confirmed the possibility of producing a pyridoxine-induced sensory neuropathy model in dogs with short-term administration.

Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration

In Theiler’s murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).