Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

ABSTRACT Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s) of blast overpressure (OP) induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM) tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L) chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

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Serotonin2 receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2665 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2665-2673 ◽

Cited By ~ 46

Author(s):

Shi-Yi Zhou ◽

Gregory J. Basura ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Receptor Antagonist ◽

Phrenic Nerve ◽

Cervical Spinal Cord ◽

Sprague Dawley ◽

Related Activity ◽

Adult Rats ◽

Cord Injury ◽

Respiratory Recovery ◽

Spinal Cord Hemisection

The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO2 levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT2A/2C-receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO2 was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT2-receptor antagonist ketanserin but not with the 5-HT2C-receptor antagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

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Temporospatial Development of Neuropathologic Findings in a Canine Model of Mucopolysaccharidosis IIIB

Veterinary Pathology ◽

10.1177/0300985820960128 ◽

2020 ◽

pp. 030098582096012

Author(s):

Tyler A. Harm ◽

Shannon J. Hostetter ◽

Ariel S. Nenninger ◽

Bethann N. Valentine ◽

N. Matthew Ellinwood ◽

...

Keyword(s):

Spinal Cord ◽

Cervical Spinal Cord ◽

Canine Model ◽

Brain Regions ◽

Large Animal ◽

Lysosomal Storage ◽

Large Animal Models ◽

Naturally Occurring ◽

The Brain ◽

Deficient Activity

Mucopolysaccharidosis (MPS) IIIB is a neuropathic lysosomal storage disease characterized by the deficient activity of a lysosomal enzyme obligate for the degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The pathogenesis of neurodegeneration in MPS IIIB is incompletely understood. Large animal models are attractive for pathogenesis and therapeutic studies due to their larger size, outbred genetics, longer lifespan, and naturally occurring MPS IIIB disease. However, the temporospatial development of neuropathologic changes has not been reported for canine MPS IIIB. Here we describe lesions in 8 brain regions, cervical spinal cord, and dorsal root ganglion (DRG) in a canine model of MPS IIIB that includes dogs aged from 2 to 26 months of age. Pathological changes in the brain included early microscopic vacuolation of glial cells initially observed at 2 months, and vacuolation of neurons initially observed at 10 months. Inclusions within affected cells variably stained positively with PAS and LFB stains. Quantitative immunohistochemistry demonstrated increased glial expression of GFAP and Iba1 in dogs with MPS IIIB compared to age-matched controls at all time points, suggesting neuroinflammation occurs early in disease. Loss of Purkinje cells was initially observed at 10 months and was pronounced in 18- and 26-month-old dogs with MPS IIIB. Our results support the dog as a replicative model of MPS IIIB neurologic lesions and detail the pathologic and neuroinflammatory changes in the spinal cord and DRG of MPS IIIB-affected dogs.

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Increased Levels of Myo-Inositol are Associated With Impaired Working Memory and Active Avoidance in Blast Neurotrauma Animals

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80466 ◽

2012 ◽

Author(s):

Sujith Sajja ◽

Shane A. Perrine ◽

Farhad Ghoddoussi ◽

Matthew P. Galloway ◽

Pamela J. VandeVord

Keyword(s):

Working Memory ◽

Clinical Symptoms ◽

Brain Regions ◽

Magic Angle Spinning ◽

Magic Angle ◽

Blast Overpressure ◽

Neurochemical Changes ◽

Angle Spinning ◽

Blast Neurotrauma ◽

Blast Induced Neurotrauma

Impaired working memory and anxiety are major clinical symptoms commonly associated with subjects exposed to blast overpressure [1–4]. Despite this association, there remains a vital need for biomarkers to help effectively diagnosis blast-induced neurotrauma (BINT). Clinically, elevated myo-inositol has been associated with several neurodegenerative disorders including dementia and elevated levels may reflect activation of microglia. In the present study, we evaluated the cognitive and behavioral changes in blast exposed animals using the novel object recognition (working memory paradigm) and light/dark (anxiety test) assessments. In addition, we used high resolution magic angle spinning H-MRS to assess neurochemical changes in the prefrontal cortex and amygdala, brain regions associated with working memory and anxiety respectively. Results suggest that exposure to blast has a significant effect on the levels of myo-inositol which appear to be linked with impaired working memory.

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Behavioral and histopathological studies of cervical spinal cord contusion injury in rats caused by an adapted weight-drop device

Asian Biomedicine ◽

10.1515/abm-2019-0019 ◽

2019 ◽

Vol 12 (4) ◽

pp. 189-198

Author(s):

Kanyaratana Bamrungsuk ◽

Anchalee Vattarakorn ◽

Namphung Thongta ◽

Kanokwan Tilokskulchai ◽

Sompol Tapechum ◽

...

Keyword(s):

Spinal Cord ◽

Cervical Spinal Cord ◽

Cervical Vertebra ◽

Thoracic Injury ◽

Sprague Dawley ◽

Behavioral Deficits ◽

Cord Injury ◽

Sh Group ◽

Weight Drop ◽

Histopathological Studies

AbstractBackgroundModels of spinal cord injury (SCI) caused by weight-drop devices to cause contusion have been used extensively, and transient behavioral deficits after thoracic injury have been demonstrated. The severity of the injury caused by the device should be mild enough to allow recovery.ObjectiveTo determine whether our adapted weight-drop device with a small tip can effectively induce mild hemicontusion at the level of the fifth cervical vertebra.MethodsWe divided 15 adult male Sprague Dawley rats into groups of 5 for the following treatments: sham (SH, laminectomy only), mild (MSCI) or severe SCI (SSCI). Behavioral tests and histopathology were used before (day 1) and after the treatment on days 3, 7, 14, 21, 28, and 35 to assess the injury.ResultsRats with SSCI showed a significant somatosensory deficit on days 3 and 7 compared with rats in the SH group, recovering by day 14. In a horizontal-ladder test of skilled locomotion, rats with SSCI showed a significant increase in error scores and percentage of total rungs used, and a decrease in the percentage of correct paw placement compared with rats in the SH group. There was greater recovery to normal paw placement by rats with MSCI than by rats with SSCI. These behavioral deficits were consistent with histopathology using hematoxylin and eosin counterstained Luxol fast blue, indicating the degree of injury and lesion area.ConclusionsMild hemicontusion caused by the adapted device can be used to evaluate SCI and provides a model with which to test the efficacy of translational therapies for SCI.

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Buspirone Dose-Response on Facilitating Forelimb Functional Recovery in Cervical Spinal Cord Injured Rats

Dose-Response ◽

10.1177/1559325821998136 ◽

2021 ◽

Vol 19 (1) ◽

pp. 155932582199813

Author(s):

Rakib Uddin Ahmed ◽

V. Reggie Edgerton ◽

Shuai Li ◽

Yong-Ping Zheng ◽

Monzurul Alam

Keyword(s):

Spinal Cord ◽

Grip Strength ◽

Dose Response ◽

Cervical Spinal Cord ◽

Dose Dependence ◽

Dorsal Column ◽

Cervical Cord ◽

Sprague Dawley ◽

Post Injury ◽

Cord Injury

Buspirone, widely used as a neuropsychiatric drug, has also shown potentials for motor function recovery of injured spinal cord. However, the optimum dosages of such treatment remain unclear. In this study, we investigated the dose-response of Buspirone treatment on reaching and grasping function in cervical cord injured rats. Seventeen adult Sprague-Dawley rats were trained to reach and grasp sugar pellets before a C4 bilateral dorsal column crush injury. After 1 week post-injury, the rats were divided into 3 groups to receive 1 of 3 different dosages of Buspirone (i.p., 1 dose/day: 1.5, n = 5; 2.5, n = 6 and 3.5 mg/kg b.w., n = 6). Forelimb reaching and grip strength test were recorded once per week, within 1 hour of Buspirone administration for 11 weeks post-injury. Different dose groups began to exhibit differences in reaching scores from 4 weeks post-injury. From 4-11 weeks post-injury, the reaching scores were highest in the lowest-dose group rats compared to the other 2 dose groups rats. Average grip strength was also found higher in the lowest-dose rats. Our results demonstrate a significant dose-dependence of Buspirone on the recovery of forelimb motor functions after cervical cord injury with the best performance occurring at the lowest dose tested.

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Emergency Closed Reduction of a C4/5 Fracture Dislocation with Complete Paraplegia Resulting in Profound Neurologic Recovery

Case Reports in Orthopedics ◽

10.1155/2013/272865 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3

Author(s):

Christian W. Müller ◽

Sebastian Decker ◽

Roland Thietje ◽

Christian Krettek

Keyword(s):

Spinal Cord ◽

Clinical Practice ◽

Animal Studies ◽

Spinal Cord Injuries ◽

Cervical Spinal Cord ◽

Neurological Deficits ◽

Fracture Dislocation ◽

Neurologic Recovery ◽

Horse Riding ◽

Walking Aids

Introduction. Cervical spinal cord injuries due to traumatic fractures are associated with persistent neurological deficits. Although clinical evidence is weak, early decompression, defined as <24–72 h, has been frequently proposed. Animal studies show better outcomes after early decompression within one hour or less, which can hardly ever be achieved in clinical practice.Case Presentation. A 37-year-old patient was hospitalized after being hit by a shying horse. After diagnosis of C4/5 fracture dislocation and complete paraplegia, she was intubated and sedated with deep relaxation. Emergency reduction was performed at approximately 120 minutes after trauma. Subsequently, a standard anterior decompression, discectomy, and fusion were carried out. She was then transferred to a specialized rehabilitation hospital. Her neurologic function improved from AIS grade A on admission to grade B postoperatively and grade D after four months of rehabilitation. One year after the accident, she was ambulatory without walking aids and restarted horse riding.Discussion and Conclusion. Rarely in clinical practice, decompression of the spine canal can be performed as early as in this case. This case highlights the potential benefit of utmost early reduction in cervical fracture dislocations with compression of the spinal cord.

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C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00899.2007 ◽

2008 ◽

Vol 295 (5) ◽

pp. R1519-R1528 ◽

Cited By ~ 24

Author(s):

XiaoHui Ding ◽

Fang Hua ◽

Kristopher Sutherly ◽

Jeffrey L. Ardell ◽

Carole A. Williams

Keyword(s):

Spinal Cord ◽

Myocardial Ischemia ◽

Dorsal Horn ◽

Cervical Spinal Cord ◽

Ibotenic Acid ◽

Opioid Antagonist ◽

Sprague Dawley ◽

Thoracic Spinal Cord ◽

Central Processing ◽

Thoracic Spinal

During myocardial ischemia, the cranial cervical spinal cord (C1–C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I–V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the κ-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.

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Attenuation of the pulmonary chemoreflex following acute cervical spinal cord injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.01370.2013 ◽

2014 ◽

Vol 116 (7) ◽

pp. 757-766 ◽

Cited By ~ 11

Author(s):

I-Lun Tsai ◽

Kun-Ze Lee

Keyword(s):

Spinal Cord ◽

Spinal Injury ◽

Cervical Spinal Cord ◽

Respiratory Response ◽

Sprague Dawley ◽

C Fibers ◽

Cord Injury ◽

Respiratory Airflow ◽

C Fiber ◽

Spontaneously Breathing

Bronchopulmonary C fibers are the primary chemosensitive afferents in the lung. The activation of bronchopulmonary C fibers evokes the pulmonary chemoreflex, which is characterized by apnea, hypotension, and bradycardia and is a critical reflex that modulates cardiorespiratory responses under physiological and pathological conditions. The present study was designed to investigate whether the pulmonary chemoreflex is altered following acute cervical spinal injury. A unilateral hemisection (Hx) or laminectomy (uninjured) in the second cervical spinal cord was performed in adult male Sprague-Dawley rats. The pulmonary chemoreflex induced by intrajugular capsaicin administration was evaluated by measuring respiratory airflow in spontaneously breathing rats and phrenic nerve activity in mechanically ventilated rats. Capsaicin treatment evoked a cessation of respiratory airflow and phrenic bursting in uninjured animals, but not in C2Hx animals. To clarify whether the attenuation of the pulmonary chemoreflex in C2Hx animals is restricted to capsaicin-induced stimuli, or generally applied to other stimuli that excite bronchopulmonary C fibers, another bronchopulmonary C-fiber stimulant (phenylbiguanide) was used to evoke the pulmonary chemoreflex in spontaneously breathing rats. We observed that phenylbiguanide-induced apnea was also blunted in C2Hx animals, suggesting that the respiratory response induced by bronchopulmonary C-fiber activation was attenuated following acute cervical spinal Hx. The blunted inhibitory respiratory response may represent a compensatory respiratory plasticity to preserve the breathing capacity and may also reduce the capability of preventing inhaled irritants in this injured condition.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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