Dorsal Cord Research Articles

Spatiotemporal control of a novel synaptic organizer molecule.

Synapse formation is a process tightly controlled in space and time. How gene regulatory mechanisms specify spatial and temporal aspects of synapse formation is not well understood. In the nematode C.elegans, two subtypes of the D-type inhibitory motor neuron (MN) classes, the dorsal D (DD) and ventral D (VD) neurons, extend axons along both the dorsal and ventral nerve cords 1. The embryonically generated DD MNs initially innervate ventral muscles in the first (L1) larval stage and receive their synaptic input from cholinergic MNs in the dorsal cord. They rewire by the end of the L1 molt to innervate dorsal muscles and to be innervated by newly formed ventral cholinergic MNs 1. VD MNs develop after the L1 molt; they take over the innervation of ventral muscles and receive their synaptic input from dorsal cholinergic MNs. We show here that the spatiotemporal control of synaptic wiring of the D-type neurons is controlled by an intersectional transcriptional strategy in which the UNC-30 Pitx-type homeodomain transcription factor acts together in embryonic and early larval stages with the temporally controlled LIN-14 transcription factor to prevent premature synapse rewiring of the DD MNs and, together with the UNC-55 nuclear hormone receptor, to prevent aberrant VD synaptic wiring in later larval and adult stages. A key effector of this intersectional transcription factor combination is a novel synaptic organizer molecule, the single immunoglobulin domain protein OIG-1. OIG-1 is perisynaptically localized along the synaptic outputs of the D-type MNs in a temporally controlled manner and is required for appropriate selection of both pre- and post-synaptic partners.

Back Pain and Inability to Walk in a Young Girl

A 20-year-old woman presented to the emergency department (ED) with progressive weakness, paresthesia, and back pain lasting for 8 days. She was conscious and her vital signs were normal. Her past medical history was unremarkable. No abnormality was found on radiography and computed tomography (CT). However, magnetic resonance imaging (MRI) showed an intramedullary mass at the dorsal cord at approximately the T8-T9 level, accompanied by mild perilesional edema. Consequently, the patient was diagnosed with hemangioma. The patient underwent preoperative embolization, with minimal bleeding during surgery. (JAEM 2015; 14: 47-8)

Hybrids between the Florida amphioxus (Branchiostoma floridae) and the Bahamas lancelet (Asymmetron lucayanum): developmental morphology and chromosome counts.

The cephalochordate genera Branchiostoma and Asymmetron diverged during the Mesozoic Era. In spite of the long separation of the parental clades, eggs of the Florida amphioxus, B. floridae, when fertilized with sperm of the Bahamas lancelet, A. lucayanum (and vice versa), develop through embryonic and larval stages. The larvae reach the chordate phylotypic stage (i.e., the pharyngula), characterized by a dorsal nerve cord, notochord, perforate pharynx, and segmented trunk musculature. After about 2 weeks of larval development, the hybrids die, as do the A. lucayanum purebreds, although all were eating the same algal diet that sustains B. floridae purebreds through adulthood in the laboratory; it is thus unclear whether death of the hybrids results from incompatible parental genomes or an inadequate diet. The diploid chromosome count in A. lucayanum and B. floridae purebreds is, respectively, 34 and 38, whereas it is 36 in hybrids in either direction. The hybrid larvae exhibit several morphological characters intermediate between those of the parents, including the size of the preoral ciliated pit and the angles of deflection of the gill slits and anus from the ventral midline. Based on the time since the two parent clades diverged (120 or 160 million years, respectively, by nuclear and mitochondrial gene analysis), the cross between Branchiostoma and Asymmetron is the most extreme example of hybridization that has ever been unequivocally demonstrated among multicellular animals.

The zinc finger RNA binding protein, ZFR, contributes to axon guidance in Caenorhabditis elegans

ZFR is an ancient and highly conserved chromosome-associated protein from nematodes to mammals, embryologically expressed in most species, with the exception of the nematode Caenorhabditis elegans. The ZFR encodes zinc and RNA binding protein, and in rat, the nuclear-cytoplasmic shuttling ZFR has been found with transport and translation-associated RNA granule-like structures in the somatodendritic compartments of hippocampal neurons. The majority of axons cross the midline before projecting to their contralateral synaptic target and this crossing decision is under tight control. Molecular factors contributing to these processes have been identified, although the mechanisms are not fully understood. In this study, we tested the role of ceZFR in axon guidance using ceZfr RNAi-treated animals to analyse axon midline crossing, axon fasciculation and cord commissures. In adult stages, RNAi-induced depletion of the ceZfr transcript leads to several phenotypes related to axon guidance. A midline crossing defect was observed in the ventral nerve cord (VNC) in axon type D, DD/VD motoneuron axons and axon type 1, interneuron axons. We further detected a dorsal nerve cord (DNC) axon fasciculation. Some ceZfr RNAi-treated animals revealed that cord commissures fail to reach their synaptic target. We provide evidence that ceZFR has a role in axon guidance. When Zfr was depleted by RNAi, the phenotypes are characterized by defects in axon midline crossing, axon defasciculation and cord commissures. Our results thus support the hypothesis that ZFR has essential roles during neurogenesis, and could support early steps of RNA transport and localization through RNA granule formation in the nucleus and/or to their nucleo-cytoplasmic shuttling.

Penetrating intradural foreign body without neurological loss: A case report

The annual incidence of traumatic spinal cord injury worldwide is 35 patients per million populations, with young males inflicted with penetrating spinal injuries representing the more common group. About 76% of the patients with penetrating spinal trauma are found to have neurologic deficit. Non-missile penetrating injuries involving the paraspinal cord region present with no neurologic deficit. Intradural penetrating spinal injury without any neurologic deficit is thus rare, especially in the thoracic or cervical region. To the best of our knowledge, after the case reported by Li Xinning et al, it is the second case report where there is intradural penetrating injury in the dorsal cord region with no neurologic deficit.

Some Morphological Studies on Prostata (Prostate Gland) of Buffalo Bull (Bos Bubalis L.)

The objective of this research was to describetheanatomical and histological structure of the prostate gland in buffalo bulls. This study was carried out on the prostate gland of 25 animals. The gland consisted of two parts; Corpus prostatae and Pars disseminate prostatae. The shape of the former part was variable (band like, two lobed connected by an isthmus (Isthmus prostatae) and three lobed gland). It was situated transversally on the dorsal aspect of the pelvic urethra just caudal to the dorsal fibrous cord of the vesicular gland. Pars disseminata prostatae occupied in the entire length of the pelvic urethra. Microscopically, the capsuleof the gland was fiberomuscular in nature. Fiberomuscular septa arose from the capsule dividing the gland into lobes. The latter septa gave rise of fiberoelastic septulae, which dividing the lobes into lobules. The prostatic secretory end-pieces were of ubule-alveolar type, which were lined with simple cuboidal epithelium. These cells reacted positively with PAS and alcian blue stains. The intralobular ducts were lined with simple cuboidal epithelium, changed into simple columnar in the interlobular ducts and transitional type in the main excretory ducts, at their opening in the pelvic urethra.

Spinal ephrinB/EphB signalling contributed to remifentanil-induced hyperalgesia via NMDA receptor.

BackgroundOne of the major unresolved issues in treating pain is the paradoxical hyperalgesia produced by opiates, and accumulating evidence implicate that EphBs receptors and ephrinBs ligands are involved in mediation of spinal nociceptive information and central sensitization, but the manner in which ephrinB/EphB signalling acts on spinal nociceptive information networks to produce hyperalgesia remains enigmatic. The objective of this research was to investigate the role of ephrinB/EphB signalling in remifentanil-induced hyperalgesia (RIH) and its downstream effector.MethodsWe characterized the remifentanil-induced pain behaviours by evaluating thermal hyperalgesia and mechanical allodynia in a rat hind paw incisional model. Protein expression of EphB1 receptor and ephrinB1 ligand in spinal dorsal horn cord was determined by Western blotting, and Fos was determined by immunohistochemistry assay, respectively. To figure out the manner in which ephrinB/EphB signalling acts with N-methyl-d-aspartic acid (NMDA) receptor, we used MK-801, an antagonist of NMDA receptor, trying to suppressed the hyperalgesia induced by ephrinB1-Fc, an agonist of ephrinB/EphB.ResultsContinuing infusion of remifentanil produced a thermal hyperalgesia and mechanical allodynia, which was accompanied with increased protein expression of spinal-level EphB1 receptor, ephrinB1 ligand and Fos; what appeared above was suppressed by pretreatment with EphB1-Fc, an antagonist of ephrinB/EphB or MK-801, and increased pain behaviours induced by intrathecal injection of ephrinB1-Fc, an agonist of ephrinB/EphB, were suppressed by MK-801.ConclusionsOur findings indicated that ephrinB/EphB signalling is involved in RIH. EphrinB/EphB signalling might be the upstream of NMDA receptor.What's already known about this topic?EphBs receptors and ephrinBs ligands are involved in mediation of spinal nociceptive information and central sensitization.The combination of EphB receptor and N-methyl-d-aspartic acid receptor induces long-term potentiation that is critical for causing excitation of spinal neuron and pain hyperalgesia.What does this study add?EphrinB/EphB signalling is involved in remifentanil-induced hyperalgesia (RIH).EphrinB/EphB signalling might be the upstream of N-methyl-d-aspartic acid receptor in RIH.

Proteolytic Processing of the Extracellular Scaffolding Protein LEV-9 Is Required for Clustering Acetylcholine Receptors

Correct positioning of neurotransmitter-gated receptors at postsynapses is essential for synaptic transmission. At Caenorhabditis elegans neuromuscular junctions, clustering of levamisole-sensitive acetylcholine receptors (L-AChRs) requires the muscle-secreted scaffolding protein LEV-9, a multidomain factor containing complement control protein (CCP) modules. Here we show that LEV-9 needs to be cleaved at its C terminus to exert its function. LEV-9 cleavage is not required for trafficking nor secretion but directly controls scaffolding activity. The cleavage site is evolutionarily conserved, and post-translational cleavage ensures the structural and functional decoupling between different isoforms encoded by the lev-9 gene. Data mining indicates that most human CCP-containing factors are likely cleaved C-terminally from CCP tandems, suggesting that not only domain architectures but also cleavage location can be conserved in distant architecturally related proteins.

Herniation of spinal cord into nerve root avulsion pseudomeningocele: A rare cause of delayed progressive neurological deficit

We present a patient with old traumatic right brachial plexus injury, who developed progressive neurological deterioration 4 years after the initial injury. On magnetic resonance imaging (MRI), herniation of the upper dorsal cord was noted into a post-traumatic pseudomeningocele. Though the herniation of cord into a post-traumatic pseudomeningocele is very rare, it should be suspected in cases of delayed progressive myelopathy. A three dimensional (3-D) T2-weighted sequence such as Sampling Perfection with Application optimized Contrasts using different flip angle Evolution (SPACE) or constructive interference in steady state (CISS) provides optimal visualization of the herniated cord and helps in surgical planning.

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug–induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

Changes of GTP cyclohydrolase I and neuronal apoptosis in rat spinal dorsal cord induced by sciatic nerve injury

It has been reported that the expression of GTP cyclohydrolase I (GCH1) and neuronal apoptosis in dorsal root ganglion (DRG) is related to the generation of neuropathic pain. In this study, we hypothesize that GCH1 protein and neuronal apoptosis in rat spinal dorsal horn may also increase after chronic sciatic nerve injury. To establish the neuropathic pain model, we slightly ligated the right sciatic nerve of experimental rats. Mechanical allodynia was observed in CCI group on the 3rd day postoperatively determined by the Von Frey test, and it lasted until the 14th day after operation. No matter which method we used, western blotting or immunohistochemistry analysis, they all showed the enhancement of GCH1 protein in spinal dorsal horn on the 3rd, 7th, and 14th days after operation due to the sciatic nerve injury (P < 0.05). The apoptosis of nerve cells also increased evidently compared with sham group detected by TUNEL staining (P < 0.05). Therefore, the data suggested that along with mechanical allodynia caused by peripheral nerve injury, both GCH1 level and apoptosis index of nerve cells in spinal dorsal horn was elevated, which might also contribute to the generation of neuropathic pain.

Effect of Electroacupuncture Intervention on Expression of CGRP, SP, COX-1, and PGE2 of Dorsal Portion of the Cervical Spinal Cord in Rats with Neck-Incision Pain

The present study was aimed to determine if cervicospinal substance P (SP) and its neurokinin-1 receptor (NK-1R), calcitonin gene-related peptide (CGRP), cyclooxygenase-1 (COX-1), and prostaglandin E2 (PGE2) were involved in electroacupuncture (EA) analgesia in neck-incision pain rats. EA intervention was applied to bilateral Futu (LI18), Hegu (LI4)-Neiguan (PC6), and Zusanli (ST36)-Yanglingquan (GB34) for 30 min. Cervicospinal SP and CGRP immunoactivity was detected by immunofluorescence technique, NK-1R and COX-1 protein and mRNA expression levels were determined using Western blot and real-time PCR, respectively, and PGE2 content was measured using ELISA. Outcomes indicated that EA of EA-LI18 and LI4-PC6 (not ST36-GB34) significantly suppressed neck-incision induced decrease of thermal pain threshold (P < 0.05). EA stimulation of LI18 and LI4-PC6 markedly inhibited neck-incision induced upregulation of SP and CGRP immunoactivity, NK-1 R and COX-1 mRNA and protein expression levels, as well as the increase of PGE2 content in the dorsal cervicospinal cord (P < 0.05). These findings showed that LI18 and LI4-PC6 EA stimulation-induced downregulation of SP, CGRP, NK-1R, COX-1, and PGE2 levels in the dorsal cervicospinal cord may contribute to their effects in relieving neck-incision pain. This study highlights the targets of EA intervention for reducing post-thyroid-surgery pain for the first time.

Incarcerated spinal cord: A preventable surgical debacle

Incarcerated spinal cord: A preventable surgical debacle

The enigma of dorsal cord migration after cervical laminectomy: A radiological entity or something else?

The enigma of dorsal cord migration after cervical laminectomy: A radiological entity or something else?

Vivax Malaria Presenting with Myelitis: A Rare Complication

Neurological complications may occur with the Plasmodium falciparum infection. However, the association of neurological manifestations with vivax malaria remains doubtful. Of late, there are isolated case reports/studies which have implicated P. vivax in the pathogenesis of severe malaria which is characterized by the features of different organ dysfunctions, which were previously thought to be caused by P. falciparum alone. Though several case studies have mentioned the association of the P. vivax infection with cerebral malaria, a causal correlation has yet to be established. Dorsal cord myelitis (which leads to paraplegia) during the febrile illness, is rarely described in association with vivax malaria, though there are reports on the Post Malaria Neurological Syndrome (PMNS) and acute disseminated encephalomyelitis following vivax malaria. We are reporting a case of P. Vivax malaria which presented with myelitis, which responded well to the antimalarial treatment.

Genetic Interactions Between UNC-17/VAChT and a Novel Transmembrane Protein in Caenorhabditis elegans

The unc-17 gene encodes the vesicular acetylcholine transporter (VAChT) in Caenorhabditis elegans. unc-17 reduction-of-function mutants are small, slow growing, and uncoordinated. Several independent unc-17 alleles are associated with a glycine-to-arginine substitution (G347R), which introduces a positive charge in the ninth transmembrane domain (TMD) of UNC-17. To identify proteins that interact with UNC-17/VAChT, we screened for mutations that suppress the uncoordinated phenotype of UNC-17(G347R) mutants. We identified several dominant allele-specific suppressors, including mutations in the sup-1 locus. The sup-1 gene encodes a single-pass transmembrane protein that is expressed in a subset of neurons and in body muscles. Two independent suppressor alleles of sup-1 are associated with a glycine-to-glutamic acid substitution (G84E), resulting in a negative charge in the SUP-1 TMD. A sup-1 null mutant has no obvious deficits in cholinergic neurotransmission and does not suppress unc-17 mutant phenotypes. Bimolecular fluorescence complementation (BiFC) analysis demonstrated close association of SUP-1 and UNC-17 in synapse-rich regions of the cholinergic nervous system, including the nerve ring and dorsal nerve cords. These observations suggest that UNC-17 and SUP-1 are in close proximity at synapses. We propose that electrostatic interactions between the UNC-17(G347R) and SUP-1(G84E) TMDs alter the conformation of the mutant UNC-17 protein, thereby restoring UNC-17 function; this is similar to the interaction between UNC-17/VAChT and synaptobrevin.

Spinal Intramedullary Lipoma: A Rare Cause of Rapidly Progressive Quadriparesis

Spinal intramedullary lipoma is rare accounting for 1% of all spinal tumours with usual location in the cervicothoracic region and usually associated with spinal dysraphism. These tumours usually have a slowly progressive indolent course. Our patient a 19 year young male presented with 2 months history of neck pain and acute onset rapidly progressive spastic quadriparesis with sensory level at T4. He did not have spinal dysgraphism. MRI spine revealed intramedullary lesions extending from cervicomedullary junction to upper dorsal cord which was hyperintense on T1 and T2 weighted images. Patient was subsequently operated and histopathology of the resected mass showed well circumscribed lesion composed of mature adipose tissue suggestive of lipoma.

A new species of symbiotic flatworms, Paracatenula galateia sp. nov. (Platyhelminthes: Catenulida: Retronectidae) from Belize (Central America)

Paracatenula galateia sp. nov. is a mouthless marine catenulid platyhelminth with bacterial intracellular endosymbionts. The worms live in shallow back-reef sands in the Belize Barrier Reef system and are distinguished from the four previously described members of the genus by their large size combined with a ribbon-shaped body and characteristic bipartite inclusions in cells, which are interpreted as sperm. The bacteria are presumed to be sulphur-oxidizing chemoautotrophs. They are found in bacteriocytes which fill the body region (‘trophosome region’) posterior to the brain, whereas the anterior part of the worm (rostrum) is bacteria-free. Phalloidin staining reveals a delicate system of subepitheliar circular and longitudinal muscles and dorsoventral fibres. The serotonergic nervous system consists of a brain at the base of the rostrum and longitudinal fibres extending both anteriorly and posteriorly, the latter being concentrated in a structure called the ‘dorsal cord’.

Hagfish, Genome Duplications, and RFamide Neuropeptide Evolution

As a phylum, the chordates are remarkably similar in terms of body plan design compared with many of the other major phyla of metazoans. The minimal features for placement within the phylum are a dorsal nerve cord and a notochord and pharyngeal gills slits at some point in the developmental life history of the organism (1). As shown in Fig. 1A, chordates can be initially segregated based on whether the organism lacks an internal cartilaginous or bony skeleton (protochordates; such as Amphioxus or the tunicates) or have an internal skeleton (subphylum Vertebrata). The vertebrates can be further separated into those organisms that lack a hinged jaw (superclass Agnatha; such as the hagfishes or lampreys) and those organisms that have a hinged jaw (superclass Gnathostoma; such as the cartilaginous fishes, bony fishes, amphibians, reptiles, birds, and mammals). As indicated from the fossil record, the ancestral protochordates most likely emerged during the Cambrian Period, some 550 million years ago (MYA) (2), and were followed in relatively quick succession by the ancestral agnathan vertebrates (late Ordovician Period; 450 MYA), and later the ancestral gnathostomes (Silurian Period 420 MYA) (3). Although the external and internal morphological design of the vertebrates (agnathans and gnathostomes) is based on common themes, there are features of the chordates that clearly have undergone considerable change during the evolution of the phylum. Two of these features, the diversity of gene families, and the interactions between the brain and pituitary, are considered in the article by Osugi et al. (4) in this issue of Endocrinology on the evolution, characterization, and localization of RFamide peptides in the central nervous system (CNS) of a hagfish. Why study hagfish, and what information on neuropeptide gene family evolution and brain/pituitary interactions can be gleaned from these organisms?

A Perimotor Framework Reveals Functional Segmentation in the Motoneuronal Network Controlling Locomotion inCaenorhabditis elegans

The neuronal connectivity dataset of the nematode Caenorhabditis elegans attracts wide attention from computational neuroscientists and experimentalists. However, the dataset is incomplete. The ventral and dorsal nerve cords of a single nematode were reconstructed halfway along the body and the posterior data are missing, leaving 21 of 75 motoneurons of the locomotor network with partial or no connectivity data. Using a new framework for network analysis, the perimotor space, we identified rules of connectivity that allowed us to approximate the missing data by extrapolation. Motoneurons were mapped into perimotor space in which each motoneuron is located according to the muscle cells it innervates. In this framework, a pattern of iterative connections emerges which includes most (0.90) of the connections. We identified a repeating unit consisting of 12 motoneurons and 12 muscle cells. The cell bodies of the motoneurons of such a unit are not necessarily anatomical neighbors and there is no obvious anatomical segmentation. A connectivity model, composed of six repeating units, is a description of the network that is both simplified (modular and without noniterative connections) and more complete (includes the posterior part) than the original dataset. The perimotor framework of observed connectivity and the segmented connectivity model give insights and advance the study of the neuronal infrastructure underlying locomotion in C. elegans. Furthermore, we suggest that the tools used herein may be useful to interpret, simplify, and represent connectivity data of other motor systems.