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BMC Neurology Nov 2020Persistent first intersegmental artery (PFIA) is a rare anatomical variation of vertebral arteries and is an asymptomatic finding in most cases. Here we report a rare...
BACKGROUND
Persistent first intersegmental artery (PFIA) is a rare anatomical variation of vertebral arteries and is an asymptomatic finding in most cases. Here we report a rare case of cervical myelopathy caused by spinal cord compression by the PFIA.
CASE PRESENTATION
The patient was a 52-year-old man who complained of numbness and burning sensation around the neck and left shoulder area, partial weakness in the left deltoid muscle, right side thermal hypoalgesia, and disturbance of deep sensation since the past 1 year, and the symptoms had gradually worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed spinal cord compression by the left PFIA at the C1/C2 level. Because conservative treatment was ineffective, microvascular decompression (MVD) of the PFIA was performed. The left PFIA was laterally transposed using polytetrafluoroethylene (PTFE) bands and anchored to the dura mater using three PTFE bands. To achieve adequate transposition, the small blood vessels bridging the spinal cord and PFIA and the dorsal root nerve had to be sacrificed. Postoperative T2-weighted MRI showed a small hyperintense region in the lateral funiculus of the spinal cord, but no new neurological deficits were identified. In the early postoperative stage, the patient's deep sensory impairment and motor dysfunction were improved. His numbness and burning sensation almost disappeared, but slight thermal hypoalgesia remained in the lower limb.
CONCLUSION
MVD is an effective treatment for spinal cord compression caused by the PFIA, but further studies are necessary to help address technical difficulties and avoid complications.
Topics: Cervical Vertebrae; Humans; Magnetic Resonance Imaging; Male; Microvascular Decompression Surgery; Middle Aged; Spinal Cord Compression; Spinal Cord Diseases; Tomography, X-Ray Computed; Vertebral Artery
PubMed: 33143678
DOI: 10.1186/s12883-020-01976-x -
IBRO Reports Dec 2020Coordination between the urinary bladder (BL) and external urethral sphincter (EUS) is necessary for storage and elimination of urine. In rats interneuronal circuits at...
Coordination between the urinary bladder (BL) and external urethral sphincter (EUS) is necessary for storage and elimination of urine. In rats interneuronal circuits at two levels of the spinal cord (i.e., L6-S1 and L3-L4) play an important role in this coordination. In the present experiments retrograde trans-synaptic transport of pseudorabies virus (PRV) encoding fluorescent markers (GFP and RFP) was used to trace these circuits. To examine the relative localization of EUS-related and BL-related interneuronal populations we injected PRV-GFP into the EUS and PRV-RFP into the BL wall. The PRV infected populations of spinal interneurons were localized primarily in the dorsal commissure (DCM) of L6/S1 and in a hypothesized lumbar spinal coordinating center (LSCC) in L3/L4 above and lateral to central canal (CC). At both sites colocalization of markers occurred in a substantial number of labeled interneurons indicating concomitant involvement of these double-labelled neurons in the EUS- and BL-circuits and suggesting their role in EUS-BL coordination. Intense GFP or RFP fluorescent was detected in a subpopulation of cells at both sites suggesting that they were infected earlier and therefore likely to represent first order, primary interneurons that directly synapse with output neurons. Larger numbers of weakly fluorescent neurons that likely represent second order interneurons were also identified. Within the population of EUS-related first order interneurons only 3-8 % exhibited positive immunoreaction for an early transcription factor Pax2 specific to GABAergic and glycinergic inhibitory neurons suggesting that the majority of interneurons in DCM and LSCC projecting directly to the EUS motoneurons are excitatory.
PubMed: 32775758
DOI: 10.1016/j.ibror.2020.07.002 -
Brain, Behavior, and Immunity Jul 2020The pathways for peripheral-to-central immune communication (P → C I-comm) following sterile lung injury (SLI) are unknown. SLI evokes systemic and central...
The pathways for peripheral-to-central immune communication (P → C I-comm) following sterile lung injury (SLI) are unknown. SLI evokes systemic and central inflammation, which alters central respiratory control and viscerosensory transmission in the nucleus tractus solitarii (nTS). These functional changes coincide with increased interleukin-1 beta (IL-1β) in the area postrema, a sensory circumventricular organ that connects P → C I-comm to brainstem circuits that control homeostasis. We hypothesize that IL-1β and its downstream transcriptional target, cyclooxygenase-2 (COX-2), mediate P → C I-comm in the nTS. In a rodent model of SLI induced by intratracheal bleomycin (Bleo), the sigh frequency and duration of post-sigh apnea increased in Bleo- compared to saline- treated rats one week after injury. This SLI-dependent change in respiratory control occurred concurrently with augmented IL-1β and COX-2 immunoreactivity (IR) in the funiculus separans (FS), a barrier between the AP and the brainstem. At this barrier, increases in IL-1β and COX-2 IR were confined to processes that stained for glial fibrillary acidic protein (GFAP) and that projected basolaterally to the nTS. Further, FS radial-glia did not express TNF-α or IL-6 following SLI. To test our hypothesis, we blocked central COX-1/2 activity by intracerebroventricular (ICV) infusion of Indomethacin (Ind). Continuous ICV Ind treatment prevented Bleo-dependent increases in GFAP + and IL-1β + IR, and restored characteristics of sighs that reset the rhythm. These data indicate that changes in sighs following SLI depend partially on activation of a central COX-dependent P → C I-comm via radial-glia of the FS.
Topics: Animals; Area Postrema; Bleomycin; Communication; Lung Injury; Neuroglia; Rats; Rats, Sprague-Dawley
PubMed: 32097765
DOI: 10.1016/j.bbi.2020.02.006 -
Frontiers in Molecular Neuroscience 2019The corticospinal tract (CST) plays an important role in controlling voluntary movement. Because the CST has a long trajectory throughout the brain toward the spinal...
The corticospinal tract (CST) plays an important role in controlling voluntary movement. Because the CST has a long trajectory throughout the brain toward the spinal cord, many axon guidance molecules are required to navigate the axons correctly during development. Previously, we found that double-knockout (DKO) mouse embryos lacking the heparan sulfate endosulfatases, and , showed axon guidance defects of the CST owing to the abnormal accumulation of Slit2 protein on the brain surface. However, postnatal development of the CST, especially the pyramidal decussation and spinal cord projection, could not be assessed because DKO mice on a C57BL/6 background died soon after birth. We recently found that DKO mice on a mixed C57BL/6 and CD-1/ICR background can survive into adulthood and therefore investigated the anatomy and function of the CST in the adult DKO mice. In DKO mice, abnormal dorsal deviation of the CST fibers on the midbrain surface persisted after maturation of the CST. At the pyramidal decussation, some CST fibers located near the midline crossed the midline, whereas others located more laterally extended ipsilaterally. In the spinal cord, the crossed CST fibers descended in the dorsal funiculus on the contralateral side and entered the contralateral gray matter normally, whereas the uncrossed fibers descended in the lateral funiculus on the ipsilateral side and entered the ipsilateral gray matter. As a result, the CST fibers that originated from 1 side of the brain projected bilaterally in the DKO spinal cord. Consistently, microstimulation of 1 side of the motor cortex evoked electromyogram responses only in the contralateral forelimb muscles of the wild-type mice, whereas the same stimulation evoked bilateral responses in the DKO mice. The functional consequences of the CST defects in the DKO mice were examined using the grid-walking, staircase, and single pellet-reaching tests, which have been used to evaluate motor function in mice. Compared with the wild-type mice, the DKO mice showed impaired performance in these tests, indicating deficits in motor function. These findings suggest that disruption of genes leads to both anatomical and functional defects of the CST.
PubMed: 32038163
DOI: 10.3389/fnmol.2019.00333 -
Journal of Neurodevelopmental Disorders Dec 2019Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function....
BACKGROUND
Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS.
METHODS
Spinal cords from embryonic to adult animals were processed for gene and protein expression (immunofluorescence) to track the spatiotemporal development of excitatory and inhibitory neurons and oligodendroglia. Postnatal analyses were focused on the lumbar region due to the reflex and gait abnormalities found in Ts65Dn mice and locomotive alterations seen in people with DS.
RESULTS
Between embryonic days E10.5 and E14.5, we found a larger motor neuron progenitor domain in Ts65Dn animals containing more OLIG2-expressing progenitor cells. These disturbed progenitors are delayed in motor neuron production but eventually generate a large number of ISL1+ migrating motor neurons. We found that higher numbers of PAX6+ and NKX2.2+ interneurons (INs) are also produced during this time frame. In the adult lumbar spinal cord, we found an increased level of Hb9 and a decreased level of Irx3 gene expression in trisomic animals. This was accompanied by an increase in Calretinin+ INs, but no changes in other neuronal populations. In aged Ts65Dn animals, both Calbindin+ and ChAT+ neurons were decreased compared to euploid controls. Additionally, in the dorsal corticospinal white matter tract, there were significantly fewer CC1+ mature OLs in 30- and 60-day old trisomic animals and this normalized to euploid levels at 10-11 months. In contrast, the mature OL population was increased in the lateral funiculus, an ascending white matter tract carrying sensory information. In 30-day old animals, we also found a decrease in the number of nodes of Ranvier in both tracts. This decrease normalized both in 60-day old and aged animals.
CONCLUSIONS
We show marked changes in both spinal white matter and neuronal composition that change regionally over the life span. In the embryonic Ts65Dn spinal cord, we observe alterations in motor neuron production and migration. In the adult spinal cord, we observe changes in oligodendrocyte maturation and motor neuron loss, the latter of which has also been observed in human spinal cord tissue samples. This work uncovers multiple cellular perturbations during Ts65Dn development and aging, many of which may underlie the motor deficits found in DS.
Topics: Animals; Disease Models, Animal; Down Syndrome; Female; Gene Expression Regulation, Developmental; Homeobox Protein Nkx-2.2; Homeodomain Proteins; Male; Mice, Transgenic; Neuroglia; Neurons; Nuclear Proteins; Spinal Cord; Transcription Factors; White Matter
PubMed: 31839007
DOI: 10.1186/s11689-019-9294-9 -
Brazilian Journal of Anesthesiology... 2019Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting non-steroidal...
BACKGROUND AND OBJECTIVES
Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs like (S)-(+)-Ketoprofen, may be effective at lower intrathecal doses than parenteral ones. Preclinical safety regarding possible neurotoxicity associated with the intrathecal (S)-(+)-Ketoprofen was not evaluated. Here we analysed the neurotoxicity of intrathecally administered (S)-(+)-Ketoprofen in rats.
METHODS
A randomized placebo-controlled experimental study was conducted. Sprague-Dawley rats (250–300 g) aged 12–16 weeks were randomly divided into 2 treatments [100 and 800 μg (S)-(+)-Ketoprofen] and control (sterile water) groups. Intrathecal catheters were placed via the atlantoaxial space in anesthetized rats. Pinch-toe tests, motor function evaluations and histopathological examinations of the spinal cord and nerve roots were performed at days 3, 7 and 21. Spinal cord sections were evaluated by light microscopy for the dorsal axonal funiculus vacuolation, axonal myelin loss, neuronal chromatolysis, neuritis, meningeal inflammation, adhesions, and fibrosis.
RESULTS
Rats in all the groups exhibited normal pinch-toe testing response (score = 0) and normal gait at each observed time (motor function evaluation score = 1). Neurotoxicity was higher with treatments on days 3 and 7 than that on day 21 (2, 3, 0, = 0.044; 2, 5, 0, = 0.029, respectively). On day 7, the total scores reflecting neuronal damage were higher in the 800 μg group than those in the 100 μg and Control Groups (5, 3, 0, = 0.048, respectively).
CONCLUSION
Intrathecal (S)-(+)-Ketoprofen caused dose-dependent neurohistopathological changes in rats on days 3 and 7 after injection, suggesting that (S)-(+)-Ketoprofen should not be intrathecally administered.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Injections, Spinal; Ketoprofen; Male; Neurotoxicity Syndromes; Rats; Rats, Sprague-Dawley; Spinal Cord; Time Factors
PubMed: 31371174
DOI: 10.1016/j.bjan.2019.03.006 -
Developmental Neurobiology Nov 2018Numerous tissue transplantations have demonstrated that otocysts can develop into normal ears in any location in all vertebrates tested thus far, though the pattern of...
Numerous tissue transplantations have demonstrated that otocysts can develop into normal ears in any location in all vertebrates tested thus far, though the pattern of innervation of these transplanted ears has largely been understudied. Here, expanding on previous findings that transplanted ears demonstrate capability of local brainstem innervation and can also be innervated themselves by efferents, we show that inner ear afferents grow toward the spinal cord mostly along existing afferent and efferent fibers and preferentially enter the dorsal spinal cord. Once in the dorsal funiculus of the spinal cord, they can grow toward the hindbrain and can diverge into vestibular nuclei. Inner ear afferents can also project along lateral line afferents. Likewise, lateral line afferents can navigate along inner ear afferents to reach hair cells in the ear. In addition, transplanted ears near the heart show growth of inner ear afferents along epibranchial placode-derived vagus afferents. Our data indicate that inner ear afferents can navigate in foreign locations, likely devoid of any local ear-specific guidance cues, along existing nerves, possibly using the nerve-associated Schwann cells as substrate to grow along. However, within the spinal cord and hindbrain, inner ear afferents can navigate to vestibular targets, likely using gradients of diffusible factors that define the dorso-ventral axis to guide them. Finally, afferents of transplanted ears functionally connect to native hindbrain vestibular circuitry, indicated by eliciting a startle behavior response, and providing excitatory input to specific sets of extraocular motoneurons.
Topics: Afferent Pathways; Animals; Brain Stem; Ear, Inner; Hair Cells, Auditory; Motor Neurons; Neurons, Afferent; Rhombencephalon; Schwann Cells; Spinal Cord
PubMed: 30027559
DOI: 10.1002/dneu.22629 -
Acta Neuropathologica Sep 2017Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both...
Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.
Topics: Animals; Antibodies; Axons; Brain; Encephalomyelitis, Autoimmune, Experimental; Female; Inflammation; Nogo Proteins; Rats; Rats, Inbred Lew; Recovery of Function; Remyelination
PubMed: 28646336
DOI: 10.1007/s00401-017-1745-3 -
International Journal of Biological... 2017The pathogenesis of amyotrophic lateral sclerosis (ALS) has not been unclear yet, it might be associated with the abnormal expression and distribution of certain...
The pathogenesis of amyotrophic lateral sclerosis (ALS) has not been unclear yet, it might be associated with the abnormal expression and distribution of certain proteins. Aldehyde dehydrogenases 1A2 (ALDH1A2) was thought to be one of potential candidates. Therefore, in this study we observed and analyzed the alteration of the expression and distribution of ALDH1A2 in the spinal cord of wild-type (WT) and Tg(SOD1*G93A)1Gur mice. We compared the expression and distribution of ALDH1A2 in the different segments, anatomic regions and neural cells of spinal cord at the different stages of WT and Tg(SOD1*G93A)1Gur mice applied the methods of fluorescent immunohistochemistry and western blot. Results revealed that ALDH1A2 extensively expressed and distributed in the spinal cord of adult WT and Tg(SOD1*G93A)1Gur mice. The expression and distribution of ALDH1A2 in the white matter including the anterior, posterior and lateral funiculus were more than that in the gray matter including the central canal, the anterior and dorsal horn. ALDH1A2 majorly expressed and distributed in the astrocyte, microglial, oligodendrocyte and neuron cells. The ALDH1A2 expression significantly decreased and redistributed in some anatomic regions of spinal cord at the onset and progression stages of Tg(SOD1*G93A)1Gur mice. The expression decrease of ALDH1A2 followed with the increase of neuron cells death. This study suggested that the alteration of expression and distribution of ALDH1A2 was potentially associated with the pathogenesis of ALS.
Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Disease Progression; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons; Retinal Dehydrogenase; Spinal Cord; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 28539831
DOI: 10.7150/ijbs.19150 -
Innovative Surgical Sciences Mar 2017Axon visualization techniques are important in assessing the efficacy of interventional approaches to stimulate neural regeneration. Whereas the labeling of descending...
Axon visualization techniques are important in assessing the efficacy of interventional approaches to stimulate neural regeneration. Whereas the labeling of descending tracts in the spinal cord has been well established using the intracortical injection of biotin dextran amine (BDA), the labeling of ascending sensory fibers of the dorsal funiculus is more problematic. Fluoro-Ruby (FR; dextran tetramethylrhodamine; MW 10,000) is a bidirectional permanent tracer, but the retrograde tracing of fibers is particularly prominent, and FR is a highly sensitive tracer that can be applied in discrete injection sites. In the present report, we used FR to efficiently label ascending fibers in the dorsal columns of the rat spinal cord. After transplantation of olfactory ensheathing cells into the transected dorsal funiculus, the application of FR was able to detect regenerating ascending fibers in the spinal cord. Regenerated fibers crossing the injury site were labeled and easily identified. It is likely that the tracer was taken up by damaged fibers. As additional advantages, the labeling is resistant to photobleaching and no additional tissue processing is necessary for visualization. It can be used for as well as injections. The findings indicate that FR can be used as a reliable fluorescent marker to study ascending regenerated fibers in the spinal cord axonal regeneration.
PubMed: 31579728
DOI: 10.1515/iss-2016-0019