The role of hemorrhage following spinal-cord injury

Losey, Patrick; Young, Christopher C.; Krimholtz, E; Bordet, Régis; Anthony, Daniel C.

doi:10.1016/j.brainres.2014.04.033

Cited by 46 publications

(38 citation statements)

References 44 publications

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“…2, 3, 4, 5 Hemorrhage also accounts for activation of microglia by components derived from blood. 6, 7, 8 The iron released by lysis of red blood cells (RBCs) plays an important role in polarizing the pro-inflammatory M1 phenotype of microglia that is detrimental.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of early hemostasis on spinal cord injury in the rat

et al. 2016

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Study design:Experimental study.Objectives:To investigate the effect of early hemostasis on spinal cord injury (SCI).Setting:Fourth Military Medical University, Xi'an, China.Methods:Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg−1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg−1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso–Beattie–Bresnahan scoring and rump height index assay were used to examine locomotion recovery.Results:Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats.Conclusion:The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice.

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Section: Introductionmentioning

confidence: 99%

Beneficial effects of early hemostasis on spinal cord injury in the rat

et al. 2016

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“…It is reasonable to speculate that blood invading spared tissue will lead to further cord damage. Per se , blood infiltrating CNS tissue is toxic [4,6,14,47]. For this reason, the paradigm of SSAD, that does not produce such potentially damaging bleeding, was chosen for all subsequent studies.…”

Section: Resultsmentioning

confidence: 99%

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials

Guı́zar-Sahagún

Martínez-Cruz²,

Franco-Bourland

et al. 2017

PLoS ONE

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Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 μL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

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“…In addition to ceRNA‐related function, the potential roles of these lncRNAs in the transcriptional modulation in SCI are also worthy of future investigations. Thirdly, although many pathological alterations, such as haemorrhage, demyelination and scar formation attract great attentions to researchers and clinicians, no studies have examined the roles of lncRNAs in these processes. Meanwhile, given that a large number of lncRNAs are involved in stem cell differentiation or neurogenesis, lncRNAs alone or as modulators of stem cell transplantation could be explored for SCI rehabilitation.…”

Section: Functional Roles Of Lncrnas In Scimentioning

confidence: 99%

Long non‐coding RNAs in the spinal cord injury: Novel spotlight

et al. 2019

J Cellular Molecular Medi

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Spinal cord injury (SCI) may lead to persistent locomotor dysfunction and somatosensory disorders, which adversely affect the quality of life of patients and cause a significant economic burden to the society. The efficacies of current therapeutic interventions are still far from satisfaction as the secondary damages resulting from the complex and progressive molecular alterations after SCI are not properly addressed. Recent studies revealed that long non‐coding RNAs (lncRNAs) are abundant in the brain and might play critical roles in several nervous system disorders. At the cellular level, lncRNAs have been shown to regulate the expression of protein‐coding RNAs and hence participate in neuronal death, demyelination and glia activation. Notably, SCI is characterized by these biological processes, suggesting that lncRNAs could be novel modulators in the pathogenesis of SCI. This review describes recent progresses in the lncRNA transcriptome analyses and their molecular functions in regulating SCI progression.

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The role of hemorrhage following spinal-cord injury

Cited by 46 publications

References 44 publications

Beneficial effects of early hemostasis on spinal cord injury in the rat

Beneficial effects of early hemostasis on spinal cord injury in the rat

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials

Long non‐coding RNAs in the spinal cord injury: Novel spotlight

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