Differences between C57BL/6 and BALB/cBy Mice in Mortality and Virus Replication after Intranasal Infection with Neuroadapted Sindbis Virus

ABSTRACT Neuroadapted Sindbis virus (NSV), given intranasally, caused fatal encephalitis in 100% of adult C57BL/6 mice and 0% of BALB/cBy mice. Most C57BL/6 mice developed severe kyphoscoliosis followed by hind-limb paralysis, while BALB/cBy mice did not. In situ hybridization for detecting NSV RNA and immunohistochemistry for detecting NSV antigen indicated that virus delivered by this route infected neurons of the olfactory region and spread caudally without infection of ependymal cells. Virus antigen was more abundant and infectious virus increased more rapidly and reached higher levels in C57BL/6 mice than in BALB/cBy mice. Surprisingly, infectious virus was cleared faster in C57BL/6 mice, and this was associated with more rapid production of neutralizing antibody. However, viral RNA was cleared more slowly in C57BL/6 mice. In both mouse strains, more infectious virus was present in the lumbar spinal cord than in the cervical spinal cord. These data suggest that genetic susceptibility to fatal NSV encephalomyelitis is determined at least in part by the efficiency of viral replication and spread in the central nervous system. The differences identified in this study provide possible phenotypes for mapping genetic loci involved in susceptibility.

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Caudal-rostral progression of alpha motoneurone degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

10.1101/2020.06.27.173054 ◽

2020 ◽

Author(s):

Alastair J Kirby ◽

Thomas Palmer ◽

Richard Mead ◽

Ronaldo Ichiyama ◽

Samit Chakrabarty

Keyword(s):

Spinal Cord ◽

Cervical Spinal Cord ◽

Motor Impairment ◽

Ventral Horn ◽

Lumbar Spinal Cord ◽

List Type ◽

Spatial Trend ◽

Transgenic Expression ◽

Spinal Segments ◽

Lumbar Spinal

AbstractMice with transgenic expression of human SOD1G93A are a widely used model of ALS, with a caudal-rostral progression of motor impairment. Previous studies have quantified the progression of motoneurone (MN) degeneration based on size, even though alpha (α-) and gamma (γ-) MNs overlap in size. Therefore, using molecular markers and synaptic inputs, we quantified the survival of α-MNs and γ-MNs at the lumbar and cervical spinal segments of 3- and 4-month SOD1G93A mice, to investigate whether there is a caudal-rostral progression of MN death. By 3-months, in the cervical and lumbar spinal cord, there was α-MN degeneration with complete γ-MN sparing. At 3-months the cervical spinal cord had more α-MNs per ventral horn than the lumbar spinal cord, in SOD1G93A mice. A similar spatial trend of degeneration was observed in the corticospinal tract, which remained intact in the cervical spinal cord at 3- and 4-months of age. These findings agree with the corticofugal synaptopathy model, that α-MN and CST of the lumbar spinal cord are more susceptible to degeneration in SOD1G93A mice. Hence, there is spatial and temporal caudal-rostral progression of α-MN and CST degeneration in SOD1G93A mice.HighlightsSOD1G93A mice display a caudal-rostral progression of motor impairment.Lumbar spinal cord of SOD1G93A mice has an enhanced susceptibility to degeneration.SOD1G93A mice exhibit a caudal-rostral progression of α-MN and CST degeneration

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Functional and Structural Changes in the Corticospinal Tract of Streptozotocin-Induced Diabetic Rats

International Journal of Molecular Sciences ◽

10.3390/ijms221810123 ◽

2021 ◽

Vol 22 (18) ◽

pp. 10123

Author(s):

Ken Muramatsu ◽

Satoshi Shimo ◽

Toru Tamaki ◽

Masako Ikutomo ◽

Masatoshi Niwa

Keyword(s):

Spinal Cord ◽

Conduction Velocity ◽

Corticospinal Tract ◽

Morphological Changes ◽

Cervical Spinal Cord ◽

Diabetic Animal ◽

Lumbar Spinal Cord ◽

Dorsal Funiculus ◽

Lumbar Spinal ◽

G Ratio

This study aimed to reveal functional and morphological changes in the corticospinal tract, a pathway shown to be susceptible to diabetes. Type 1 diabetes was induced in 13-week-old male Wistar rats administered streptozotocin. Twenty-three weeks after streptozotocin injection, diabetic animals and age-matched control animals were used to demonstrate the conduction velocity of the corticospinal tract. Other animals were used for morphometric analyses of the base of the dorsal funiculus of the corticospinal tract in the spinal cord using both optical and electron microscopy. The conduction velocity of the corticospinal tract decreased in the lumbar spinal cord in the diabetic animal, although it did not decrease in the cervical spinal cord. Furthermore, atrophy of the fibers of the base of the dorsal funiculus was observed along their entire length, with an increase in the g-ratio in the lumbar spinal cord in the diabetic animal. This study indicates that the corticospinal tract fibers projecting to the lumbar spinal cord experience a decrease in conduction velocity at the lumbar spinal cord of these axons in diabetic animals, likely caused by a combination of axonal atrophy and an increased g-ratio due to thinning of the myelin sheath.

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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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Lipomeningocele associated with diplomyelia in a dog

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.15654/tpk-170751 ◽

2018 ◽

Vol 46 (05) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Nele Ondreka ◽

Sara Malberg ◽

Emma Laws ◽

Martin Schmidt ◽

Sabine Schulze

Keyword(s):

Spinal Cord ◽

Neurological Status ◽

Split Cord Malformation ◽

Lumbar Spinal Cord ◽

Histopathological Diagnosis ◽

Type I ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Subcutaneous Mass ◽

Lumbar Spinal

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.

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Faculty Opinions recommendation of Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13601956.14995056 ◽

2012 ◽

Author(s):

Serge Rossignol

Keyword(s):

Spinal Cord ◽

Functional Organization ◽

Lumbar Spinal Cord ◽

Newborn Rat ◽

Lumbar Spinal

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Faculty Opinions recommendation of Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord (conus medullaris) injuries.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8263956.8692054 ◽

2011 ◽

Author(s):

Carlos Bagley

Keyword(s):

Spinal Cord ◽

Conus Medullaris ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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Aging process of the human lumbar spinal cord: A morphometric analysis

Neuropathology ◽

10.1111/j.1440-1789.1996.tb00164.x ◽

1996 ◽

Vol 16 (2) ◽

pp. 106-111 ◽

Cited By ~ 5

Author(s):

Ming Zhou ◽

Noboru Goto ◽

Chen Zhang ◽

Wei Tang

Keyword(s):

Spinal Cord ◽

Morphometric Analysis ◽

Aging Process ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury

Nature Communications ◽

10.1038/s41467-021-22137-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Marco Bonizzato ◽

Nicholas D. James ◽

Galyna Pidpruzhnykova ◽

Natalia Pavlova ◽

Polina Shkorbatova ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Stress Responses ◽

Learning Algorithm ◽

Lumbar Spinal Cord ◽

Cord Injury ◽

Potential Synergy ◽

Lumbar Spinal ◽

Deep Brain

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.

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