scholarly journals Survival and Axonal Outgrowth of the Mauthner Cell Following Spinal Cord Crush Does Not Drive Post-injury Startle Responses

2021 ◽  
Vol 9 ◽  
Author(s):  
Steven J. Zottoli ◽  
Donald S. Faber ◽  
John Hering ◽  
Ann C. Dannhauer ◽  
Susan Northen
Keyword(s):  
Spinal Cord ◽  
Control Fish ◽  
Emg Activity ◽  
M Cells ◽  
M Cell ◽  
Post Injury ◽  
Wound Site ◽  
Axonal Regrowth ◽  
Structural And Functional Properties ◽  
Cord Injury

A pair of Mauthner cells (M-cells) can be found in the hindbrain of most teleost fish, as well as amphibians and lamprey. The axons of these reticulospinal neurons cross the midline and synapse on interneurons and motoneurons as they descend the length of the spinal cord. The M-cell initiates fast C-type startle responses (fast C-starts) in goldfish and zebrafish triggered by abrupt acoustic/vibratory stimuli. Starting about 70 days after whole spinal cord crush, less robust startle responses with longer latencies manifest in adult goldfish, Carassius auratus. The morphological and electrophysiological identifiability of the M-cell provides a unique opportunity to study cellular responses to spinal cord injury and the relation of axonal regrowth to a defined behavior. After spinal cord crush at the spinomedullary junction about one-third of the damaged M-axons of adult goldfish send at least one sprout past the wound site between 56 and 85 days postoperatively. These caudally projecting sprouts follow a more lateral trajectory relative to their position in the fasciculus longitudinalis medialis of control fish. Other sprouts, some from the same axon, follow aberrant pathways that include rostral projections, reversal of direction, midline crossings, neuromas, and projection out the first ventral root. Stimulating M-axons in goldfish that had post-injury startle behavior between 198 and 468 days postoperatively resulted in no or minimal EMG activity in trunk and tail musculature as compared to control fish. Although M-cells can survive for at least 468 day (∼1.3 years) after spinal cord crush, maintain regrowth, and elicit putative trunk EMG responses, the cell does not appear to play a substantive role in the emergence of acoustic/vibratory-triggered responses. We speculate that aberrant pathway choice of this neuron may limit its role in the recovery of behavior and discuss structural and functional properties of alternative candidate neurons that may render them more supportive of post-injury startle behavior.

scholarly journals Laryngeal and swallow dysregulation following acute cervical spinal cord injury

2021 ◽  
Author(s):  
Teresa Pitts ◽  
Kimberly E Iceman ◽  
Alyssa Huff ◽  
M Nicholas Musselwhite ◽  
Michael L Frazure ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cervical Spinal Cord ◽  
Upper Airway ◽  
Emg Activity ◽  
Post Injury ◽  
Percent Change ◽  
Cord Injury ◽  
Posterior Cricoarytenoid ◽  
Diaphragm Activity

Proper function of the larynx is vital to airway protection, including swallow. While the swallow reflex is controlled by the brainstem, patients with cervical spinal cord injuries (cSCI) are likely at increased risk of disordered swallow (dysphagia) and pneumonia, and the underlying mechanisms are unknown. We aimed to determine if acute spinal cord injury would disrupt swallow function in animal models. We hypothesized that 1) loss of descending efferent information to the diaphragm would affect swallow and breathing differently, and that 2) loss of ascending spinal afferent information would alter central swallow regulation to change motor drive to the upper airway. We recorded amplitudes of laryngeal and inspiratory muscle electromyograms (EMGs), submental and pharyngeal muscle EMGs, and cardiorespiratory measures in freely breathing pentobarbital-anesthetized cats and rats. First, we assessed the effect of a lateral hemisection at the second cervical level (C2) in cats during breathing. Posterior cricoarytenoid (laryngeal abductor) EMG activity during inspiration increased nearly two-fold, indicating that inspiratory laryngeal drive increased following cSCI. Ipsilateral to the injury, the crural diaphragm EMG was significantly reduced during breathing (62 ± 25 percent change post-injury), but no animal had a complete termination of all activity; 75% of animals had an increase in contralateral diaphragm recruitment after cSCI, but this did not reach significance. Next, we assessed the effect of C2 lateral hemisection in cats during swallow. The thyroarytenoid (laryngeal adductor) and thyropharyngeus (pharyngeal constrictor) both increased EMG activity during swallow, indicating increased upper airway drive during swallow following cSCI. There was no change in the number of swallows stimulated per trial. We also found that diaphragm activity during swallow (schluckatmung) was bilaterally suppressed after lateral C2 hemisection, which was unexpected because this injury did not suppress contralateral diaphragm activity during breathing. Swallow-breathing coordination was also affected by cSCI, with more post-injury swallows occurring during early expiration. Finally, because we wanted to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the cat C2 lateral hemisection, a similar increase in inspiratory laryngeal activity (posterior cricoarytenoid) was the first feature noted after rat T1 complete spinal cord transection. In contrast to the cat C2 lateral hemisection, diaphragmatic respiratory drive increased after T1 transection in every rat (215 ± 63 percent change), and this effect was significant. Overall, we found that spinal cord injury alters laryngeal drive during swallow and breathing, and alters swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting that swallow may be more affected than breathing is by cSCI, and emphasizing the need for additional studies on laryngeal function during breathing and swallow after spinal cord injury.

scholarly journals D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiyuan Ji ◽  
Yuxin Zhang ◽  
Chen Chen ◽  
Hui Li ◽  
Bingqiang He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signal Pathways ◽  
Post Injury ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Spinal Cord Contusion

Abstract Background Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. Methods A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. Conclusion Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

scholarly journals The Histopathology of Severe Graded Compression in Lower Thoracic Spinal Cord Segment of Rat, Evaluated at Late Post-injury Phase

2021 ◽  
Author(s):  
Fedorova Jana ◽  
Kellerova Erika ◽  
Bimbova Katarina ◽  
Pavel Jaroslav
Keyword(s):  
Spinal Cord ◽  
Spontaneous Recovery ◽  
Traumatic Injury ◽  
Blue Dye ◽  
Post Injury ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Severe Traumatic Injury ◽  
Spinal Cord Segment ◽  
Cord Injury

AbstractSpontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

MSC secreted extracellular vesicles carrying TGF-beta upregulate Smad 6 expression and promote the regrowth of neurons in spinal cord injured rats

2021 ◽  
Author(s):  
Tianyu Han ◽  
Peiwen Song ◽  
Zuomeng Wu ◽  
Xiang Xia ◽  
Ying Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Extracellular Vesicles ◽  
Kinase Inhibitor ◽  
Inflammatory Factors ◽  
Type I ◽  
Post Injury ◽  
Cord Injury ◽  
Spinal Cord Injured ◽  
Feedback Regulator

Abstract Mesenchymal stem cells (MSCs) are a promising therapy for spinal cord injury (SCI) as they can provide a favorable environment for the regrowth of neurons and axons by inhibiting receptor-regulated Smads (R-Smads) in endogenous neural stem cells (NSCs). However, their mechanism of action and effect on the expression of inhibitory Smads (I-Smads) remains unclear. Here, we demonstrated that Extracellular vesicles (EVs) from MSCs were able to upregulate the Smad 6 expression by carrying TGF-β. Smad 6 knockdown in NSCs partly weakened the BMSC-EVs-induced effect on neural differentiation. In spinal cord injured rats, we found that in the acute phase of injury, the Smad 6 expression was not reduced by the treatment of TGF-β type I receptor kinase inhibitor SB431542, indicating that the Smad 6 expression was not only mediated TGF-β, the inflammatory factors and BMPs were also involved. However, in the later phase of SCI, the Smad 6 expression was reduced by the addition of SB 431542, suggesting in this phase, TGF-β played a key role on the mediation of Smad 6 expression. In addition, by immunohistochemistry staining, Hematoxylin-eosin staining and BBB scores, we revealed that the early inhibition of TGF-β did not increase the regrowth of neurons. Instead, it increased the volume of cavity and the Caspase-3 expression at 24h post-injury, leading to a wore functional outcome. In contrast the later treatment of the TGF-β inhibitor promoted the regrowth of neurons around the cavity, resulting into a better neurological outcome. Together all these results indicated that Smad 6 acts as a feedback regulator to prevents over-differentiation of NSCs to astrocytes and BMSC-EVs can upregulate Smad 6 expression by the carring TGF-β.

Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

2021 ◽  
Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
External Validation ◽  
Inpatient Rehabilitation ◽  
Spinal Cord Tissue ◽  
Light Touch ◽  
Post Injury ◽  
Data Set ◽  
Cord Injury ◽  
Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model

2021 ◽  
Author(s):  
Tetsuichi Saito ◽  
Daisuke Gotoh ◽  
Naoki Wada ◽  
Pradeep Tyagi ◽  
Tomonori Minagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Time Course ◽  
Time Dependent ◽  
Lower Urinary Tract Dysfunction ◽  
Emg Activity ◽  
Mrna Levels ◽  
Mechanosensitive Channels ◽  
Reduction Time ◽  
Cord Injury

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity as well as the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4 and 6 weeks post SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, non-voiding contractions was confirmed at 2 weeks post-SCI, and did not increase over time to 6 weeks. In 2-weeks SCI mice, EUS-EMG measurements revealed detrusor-sphincter dyssynergia (DSD), but periodic EMG reductions during bladder contraction were hardly observed. At 4 weeks, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency (VE). At 6 weeks, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of TRPV1 and ASIC1-3 in SCI mice with a decrease of ASIC2-3 at 6 weeks compared to 4 weeks whereas Piezo2 showed a slow increase at 6 weeks. Protein assay showed the SCI-induced overexpression of bladder BDNF with a time-dependent decrease post SCI. These results indicate that detrusor overactivity is established in the early phase whereas DSD is completed later at 4 weeks with an improvement at 6 weeks post SCI, and that mechanosensitive channels may be involved in the time-dependent changes.

Support of axonal regrowth by endogenous mechanisms following spinal cord injury in adult rats

2001 ◽  
Vol 21 (3) ◽  
pp. 188-202 ◽  
Author(s):  
Norman R West ◽  
Victoria LeBlanc ◽  
George H Collins
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adult Rats ◽  
Axonal Regrowth ◽  
Cord Injury

scholarly journals Effects of a Contusive Spinal Cord Injury on Spinal Motor Neuron Activity and Conduction Time in Rats

2020 ◽  
Author(s):  
Jordan A. Borrell ◽  
Dora Krizsan-Agbas ◽  
Randolph J. Nudo ◽  
Shawn B. Frost
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spike Activity ◽  
Short Latency ◽  
Neuron Activity ◽  
Emg Activity ◽  
Conduction Time ◽  
Dorsal Midline ◽  
Cord Injury ◽  
Contusion Injury

AbstractObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LON, followed by a peak response (Lp), and then falling below baseline at time LOFF. EMG responses occurred between LON and Lp (25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord motor neurons after a dorsal midline contusion injury.SignificanceThis study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

Sign in / Sign up

Export Citation Format

Share Document