scholarly journals VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review

2013 ◽  
Vol 2013 ◽  
pp. 1-28 ◽  
Author(s):  
Pablo R. Brumovsky
Keyword(s):  
Spinal Cord ◽  
Synaptic Vesicles ◽  
Morphological Analysis ◽  
Current Knowledge ◽  
Historical Account ◽  
Peripheral Neurons ◽  
Physiological Relevance ◽  
Autonomic Neurons ◽  
Vesicular Glutamate Transporters ◽  
Peripheral Sensory

Vesicular glutamate transporters (VGLUTs) are key molecules for the incorporation of glutamate in synaptic vesicles across the nervous system, and since their discovery in the early 1990s, research on these transporters has been intense and productive. This review will focus on several aspects of VGLUTs research on neurons in the periphery and the spinal cord. Firstly, it will begin with a historical account on the evolution of the morphological analysis of glutamatergic systems and the pivotal role played by the discovery of VGLUTs. Secondly, and in order to provide an appropriate framework, there will be a synthetic description of the neuroanatomy and neurochemistry of peripheral neurons and the spinal cord. This will be followed by a succinct description of the current knowledge on the expression of VGLUTs in peripheral sensory and autonomic neurons and neurons in the spinal cord. Finally, this review will address the modulation of VGLUTs expression after nerve and tissue insult, their physiological relevance in relation to sensation, pain, and neuroprotection, and their potential pharmacological usefulness.

Vasopressor support in managing acute spinal cord injury: current knowledge

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
John K. Yue ◽  
Rachel E. Tsolinas ◽  
John F. Burke ◽  
Hansen Deng ◽  
Pavan S. Upadhyayula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Current Knowledge ◽  
Acute Spinal Cord Injury ◽  
Vasopressor Support ◽  
Cord Injury

scholarly journals Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice

2021 ◽  
Vol 22 (7) ◽  
pp. 3604
Author(s):  
Nicola Alessio ◽  
Carmela Belardo ◽  
Maria Consiglia Trotta ◽  
Salvatore Paino ◽  
Serena Boccella ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vitamin D ◽  
Chronic Pain ◽  
Vitamin D Deficiency ◽  
Morphological Analysis ◽  
Pain Perception ◽  
Ex Vivo ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects

The bioactive form of vitamin .D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

scholarly journals Expression of Vesicular Glutamate Transporters in Sensory and Autonomic Neurons Innervating the Mouse Bladder

2013 ◽  
Vol 189 (6) ◽  
pp. 2342-2349 ◽  
Author(s):  
Pablo R. Brumovsky ◽  
Rebecca P. Seal ◽  
Kerstin H. Lundgren ◽  
Kim B. Seroogy ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Glutamate Transporters ◽  
Autonomic Neurons ◽  
Vesicular Glutamate Transporters

Review of clinical trials of neuroprotection in acute spinal cord injury

1999 ◽  
Vol 6 (1) ◽  
pp. E10 ◽  
Author(s):  
Charles H. Tator ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Treatment Time ◽  
Time Window ◽  
Current Knowledge ◽  
Acute Spinal Cord Injury ◽  
Randomized Controlled Studies ◽  
Cord Injury ◽  
Therapeutic Time Window

In this paper the authors review the clinical trials of neuroprotection that have been performed for the treatment of acute spinal cord injury (SCI). The biological rationale for the selection of each treatment modality is discussed with reference to current knowledge of the principles in the management of acute SCI as well as the primary and secondary injury mechanisms identified by experimental and clinical studies of the pathophysiology of acute SCI. The trials are evaluated with regard to the availability and use of accurate clinical outcome measures, and the methodologies of the trials are critically evaluated with an emphasis on prospective randomized controlled studies. A detailed description and critical analysis are provided of the results of the 10 clinical trials conducted to date in which a randomized prospective controlled design has been used. The issue of the therapeutic time window in acute SCI is discussed. To date, methylprednisolone is the only effective neuroprotective agent that has been established for use in human SCI, and the only therapeutic time window established in human SCI is a maximum trauma-to-treatment time of 8 hours.

scholarly journals Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum

2011 ◽  
Vol 519 (16) ◽  
pp. 3346-3366 ◽  
Author(s):  
Pablo R. Brumovsky ◽  
David R. Robinson ◽  
Jun-Ho La ◽  
Kim B. Seroogy ◽  
Kerstin H. Lundgren ◽  
...  
Keyword(s):  
Glutamate Transporters ◽  
Autonomic Neurons ◽  
Vesicular Glutamate Transporters

scholarly journals ASIC3-dependent spinal cord nociceptive signaling in cutaneous pain induced by lysophosphatidyl-choline

2020 ◽  
Author(s):  
Ludivine Pidoux ◽  
Kevin Delanoe ◽  
Eric Lingueglia ◽  
Emmanuel Deval
Keyword(s):  
Spinal Cord ◽  
Neuron Activity ◽  
Dorsal Spinal Cord ◽  
Spinal Cord Neurons ◽  
Lysophosphatidyl Choline ◽  
Nociceptive Pathway ◽  
Nociceptive Fibers ◽  
Cord Neuron ◽  
Peripheral Sensory

ABSTRACTLysophosphatidyl-choline (LPC), a member of the phospholipid family, has recently emerged as an interesting new player in pain. It has been proposed to mediate pain through Acid-Sensing Ion Channel 3 (ASIC3), a pain-related channel mainly expressed in peripheral sensory neurons. LPC potentiates ASIC3 current evoked by mild acidifications, but can also activate the channel at physiological pH, and its local injection in rodents evokes ASIC3-dependent pain. We combine here in vivo recordings of spinal cord neuron activity with subcutaneous LPC injection to analyze the mechanism of action associated with the LPC-induced, ASIC3-dependent pain in peripheral and spinal cord neurons. We show that a single cutaneous injection of LPC exclusively affects the nociceptive pathway. It evokes an ASIC3-dependent short-term sensitization of nociceptive fibers that drives hyperexcitability of projecting neurons within the dorsal spinal cord without apparent central sensitization.

scholarly journals Dermal macrophages set pain sensitivity by modulating tissue NGF levels through SNX25–Nrf2 signaling

2021 ◽  
Author(s):  
Tatsuhide Tanaka ◽  
Hiroaki Okuda ◽  
Yuki Terada ◽  
Ayami Isonishi ◽  
Masahiro Kitabatake ◽  
...  
Keyword(s):  
Pain Sensitivity ◽  
Pain Behavior ◽  
Mrna Synthesis ◽  
Pain Sensation ◽  
Key Factors ◽  
Transgenic Mouse Line ◽  
Sorting Nexin ◽  
Peripheral Neurons ◽  
Peripheral Sensory ◽  
Transplantation Experiments

Abstract Crosstalk between peripheral neurons and immune cells plays important roles in pain sensation. We identified sorting nexin 25 (Snx25) as a pain-modulating gene in a transgenic mouse line with reduced pain behavior. Snx25 conditional-KO (cKO) in monocyte/macrophage-lineage cells but not in the peripheral sensory neurons reduced pain responses in both normal and neuropathic conditions. Cross transplantation experiments of bone marrows between cKO and wild type (WT) mice revealed that cKO macrophages caused dull phenotype in WT mice and WT macrophages in turn increased pain behavior in cKO mice. SNX25 in dermal macrophages enhances NGF (one of the key factors in pain sensation) production by inhibiting ubiquitin-mediated degradation of Nrf2, a transcription factor that activates Ngf mRNA synthesis. We conclude that dermal macrophages set pain sensitivity by producing and secreting NGF into the dermis in addition to their host defense functions.

scholarly journals A bipedal mammalian model for spinal cord injury research: The tammar wallaby

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 921 ◽  
Author(s):  
Norman R. Saunders ◽  
Katarzyna M. Dziegielewska ◽  
Sophie C. Whish ◽  
Lyn A. Hinds ◽  
Benjamin J. Wheaton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sensory Input ◽  
Tammar Wallaby ◽  
Muscle Coordination ◽  
Thoracic Spinal Cord ◽  
Hind Limbs ◽  
Cord Injury ◽  
Trunk Posture ◽  
Peripheral Sensory

Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropus eugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7–60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.

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