Three-dimensional morphometry of spinal cord injury following polyethylene glycol treatment

2002 ◽  
Vol 205 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Bradley S. Duerstock ◽  
Richard B. Borgens
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Polyethylene Glycol ◽  
Three Dimensional ◽  
Companion Paper ◽  
Behavioral Recovery ◽  
Post Injury ◽  
Cord Injury ◽  
Peg Treatment ◽  
Spinal Cord Injured

SUMMARY We are developing a novel means of restoring function after severe acute spinal cord injury. This involves a brief application of polyethylene glycol (PEG) to the site of injury. In the companion paper, we have shown that a delayed application of PEG can produce strikingly significant physiological and behavioral recovery in 90–100 % of spinal-cord-injured guinea pigs. In the present paper, we used three-dimensional computer reconstructions of PEG-treated and sham-treated spinal cords to determine whether the pathological character of a 1-month-old injury is ameliorated by application of PEG. Using a novel isocontouring algorithm, we show that immediate PEG treatment and treatment delayed by up to 7 h post-injury statistically increased the volume of intact spinal parenchyma and reduced the amount of cystic cavitation. Furthermore, in PEG-treated animals, the lesion was more focal and less diffuse throughout the damaged segment of the spinal cord, so that control cords showed a significantly extended lesion surface area. This three-dimensional computer evaluation showed that the functional recovery produced by topical application of a hydrophilic polymer is accompanied by a reduction in spinal cord damage.

Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol

2002 ◽  
Vol 205 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Richard B. Borgens ◽  
Riyi Shi ◽  
Debra Bohnert
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Polyethylene Glycol ◽  
Guinea Pig ◽  
Topical Application ◽  
Spinal Cord Injuries ◽  
Thoracic Vertebrae ◽  
Behavioral Recovery ◽  
Thoracic Spinal Cord ◽  
Cord Injury

SUMMARY Topical application of the hydrophilic polymer polyethylene glycol (PEG) to isolated adult guinea pig spinal cord injuries has been shown to lead to the recovery of both the anatomical integrity of the tissue and the conduction of nerve impulses through the lesion. Furthermore, a brief (2 min) application of the fusogen (Mr 1800, 50 % w/v aqueous solution) to the exposed spinal cord injury in vivo can also cause rapid recovery of nerve impulse conduction through the lesion in association with functional recovery. Behavioral recovery was demonstrated using a long-tract, spinal-cord-dependent behavior in rodents known as the cutaneus trunci muscle (CTM) reflex. This reflex is observed as a contraction of the skin of the back in response to tactile stimulation. Here, we confirm and extend these preliminary observations. A severe compression/contusion injury to the exposed thoracic spinal cord of the guinea pig was performed between thoracic vertebrae 10 and 11. Approximately 7 h later, a topical application of PEG was made to the injury (dura removed) for 2 min in 15 experimental animals, and levels of recovery were compared with those of 13 vehicle-treated control animals. In PEG-treated animals, 93 % recovered variable levels of CTM functioning and all recovered some level of conduction through the lesion, as measured by evoked potential techniques. The recovered reflex was relatively normal compared with the quantitative characteristics of the reflex prior to injury with respect to the direction, distance and velocity of skin contraction. Only 23 % of the control population showed any spontaneous CTM recovery (P=0.0003) and none recovered conduction through the lesion during the 1 month period of observation (P=0.0001). These results suggest that repair of nerve membranes by polymeric sealing can provide a novel means for the rapid restoration of function following spinal cord injury.

scholarly journals Lentiviral interleukin-10 gene therapy preserves fine motor circuitry and function after a cervical spinal cord injury in male and female mice

2020 ◽  
Author(s):  
Jessica Y Chen ◽  
Emily J Fu ◽  
Paras R Patel ◽  
Hasan A Sawan ◽  
Kayla A Moss ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Interleukin 10 ◽  
Fine Motor ◽  
Behavioral Recovery ◽  
Post Injury ◽  
Cord Injury ◽  
Muscle Innervation ◽  
Anti Inflammatory

AbstractIn mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, lower motor neuron apoptosis and muscle innervation using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce lower motor neuron loss, muscle denervation, and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

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 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.

scholarly journals A combined scoring method to assess behavioral recovery after mouse spinal cord injury

2010 ◽  
Vol 67 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Ahdeah Pajoohesh-Ganji ◽  
Kimberly R. Byrnes ◽  
Gita Fatemi ◽  
Alan I. Faden
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Behavioral Recovery ◽  
Scoring Method ◽  
Mouse Spinal Cord ◽  
Cord Injury

Transplantation of collagen sponge-based three-dimensional neural stem cells cultured in the RCCS system facilitate locomotor functional recovery in spinal cord injury animals

2022 ◽  
Author(s):  
Jianwu Dai ◽  
Yunlong Zou ◽  
Yanyun Yin ◽  
Zhifeng Xiao ◽  
Yannan Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Three Dimensional ◽  
Collagen Sponge ◽  
Cellular Functions ◽  
Cord Injury ◽  
Cells Cultured

Numerous studies have indicated that microgravity induces various changes in the cellular functions of neural stem cells (NSCs), and the use of microgravity to culture tissue engineering seed cells for...

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