MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats.
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SUBMITTER: Zhou Q
PROVIDER: S-EPMC8204088 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.
| S-EPMC9402533 | biostudies-literature
Project description:Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body's H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production.
| S-EPMC4745042 | biostudies-literature
Project description:IntroductionMost cases of decompression sickness (DCS) occur soon after surfacing, with 98% within 24 hours. Recompression using hyperbaric chamber should be administrated as soon as feasible in order to decrease bubble size and avoid further tissue injury. Unfortunately, there may be a significant time delay from surfacing to recompression. The time beyond which hyperbaric treatment is non effective is unclear. The aims of the study were first to evaluate the effect of delayed hyperbaric treatment, initiated more than 48 h after surfacing for DCS and second, to evaluate the different treatment protocols.MethodsFrom January 2000 to February 2014, 76 divers had delayed hyperbaric treatment (≥48 h) for DCS in the Sagol center for Hyperbaric medicine and Research, Assaf-Harofeh Medical Center, Israel. Data were collected from their medical records and compared to data of 128 patients treated earlier than 48 h after surfacing at the same hyperbaric institute.ResultsThere was no significant difference, as to any of the baseline characteristics, between the delayed and early treatment groups. With respect to treatment results, at the delayed treatment divers, complete recovery was achieved in 76% of the divers, partial recovery in 17.1% and no improvement in 6.6%. Similar results were achieved when treatment started early, where 78% of the divers had complete recovery, 15.6% partial recovery and 6.2% no recovery. Delayed hyperbaric treatment using US Navy Table 6 protocol trended toward a better clinical outcome yet not statistically significant (OR=2.786, CI95%[0.896-8.66], p=0.07) compared to standard hyperbaric oxygen therapy of 90 minutes at 2 ATA, irrespective of the symptoms severity at presentation.ConclusionsLate recompression for DCS, 48 hours or more after surfacing, has clinical value and when applied can achieve complete recovery in 76% of the divers. It seems that the preferred hyperbaric treatment protocol should be based on US Navy Table 6.
| S-EPMC4408070 | biostudies-literature
Project description:Spinal cord injury (SCI) is a severe trauma of the central nervous system characterized by high disability and high mortality. Clinical progress has been achieved in understanding the pathological mechanism of SCI and its early treatment, but the results are unsatisfactory. In China, increasing attention has been paid to the role of traditional Chinese medicine in the treatment of SCI. In particular, extracts from the leaves of Ginkgo biloba (maidenhair tree), which have been reported to exert anti-inflammatory and antioxidant properties and repair a variety of active cellular damage, have been applied therapeutically for centuries. In this study, we established a rat SCI model to investigate the effects of Ginkgo biloba leaves on decompression at different stages of SCI. The application of Ginkgo biloba leaves during the decompression of SCI at different time points, the neurological recovery of SCI, and the underlying molecular mechanism were explored. The findings provide reliable experimental data that reveal the mechanism of GBI (Ginkgo biloba injection) in the clinical treatment of SCI.
| S-EPMC7292971 | biostudies-literature
Project description:Acute hyperbaric O2 (HBO) therapy after spinal cord injury (SCI) can reduce inflammation and increase neuronal survival. To our knowledge, it is unknown if these benefits of HBO require hyperbaric vs. normobaric hyperoxia. We used a C4 lateralized contusion SCI in adult male and female rats to test the hypothesis that the combination of hyperbaria and 100% O2 (i.e. HBO) more effectively mitigates spinal inflammation and neuronal loss, and enhances respiratory recovery, as compared to normobaric 100% O2. Experimental groups included spinal intact, SCI no O2 therapy, and SCI + 100% O2 delivered at normobaric pressure (1 atmosphere, ATA), or at 2- or 3 ATA. O2 treatments lasted 1-h, commenced within 2-h of SCI, and were repeated for 10 days. The spinal inflammatory response was assessed with transcriptomics (RNAseq) and immunohistochemistry. Gene co-expression network analysis showed that the strong inflammatory response to SCI was dramatically diminished by both hyper- and normobaric O2 therapy. Similarly, both HBO and normobaric O2 treatments reduced the prevalence of immunohistological markers for astrocytes (glial fibrillary acidic protein) and microglia (ionized calcium binding adaptor molecule) in the injured spinal cord. However, HBO treatment also had unique impacts not detected in the normobaric group including upregulation of an anti-inflammatory cytokine (interleukin-4) in the plasma, and larger inspiratory tidal volumes at 10-days (whole body-plethysmography measurements). We conclude that normobaric O2 treatment can reduce the spinal inflammatory response after SCI, but pressured O2 (i.e., HBO) provides further benefit.
| S-EPMC10729514 | biostudies-literature
Project description:BackgroundSpinal cord injury (SCI) can be caused by a variety of factors and its severity can range from a mild concussion to a complete severing of the spinal cord. Τreatment depends on the type and severity of injury, the patient's age and overall health. Reduction of dislocated or fractured vertebrae via closed manipulation or surgical procedures, fixation and removal of bony fragments and debris that compromise the spinal canal are indicated for decompression of the spinal cord and stabilization of the spine. However, when there is no obvious traumatic obstruction of spinal canal, the question arises as to whether laminectomy is needed to be performed to improve neurological outcome.MethodsA literature review covering all indexed studies published between 2013 and 2023 was performed using keywords to identify the patient group of interest (spinal cord injury, SCI, spinal cord trauma, cervical, thoracic, lumbar, thoracolumbar),central cord syndrome (CCS) and the interventions (laminectomy, laminoplasty, decompression, duroplasty).ResultsThis review includes6 observational studies investigating the outcome of posterior spinal decompression in patients suffering from spinal cord injury without traumatic spinal cord stenosis. Most patients already had degenerative stenosis. From a total of 202, 151 patients (74.7%) improved neurologically by at least one grade at ASIA scale, after being treated with either laminectomy, laminoplasty, duroplasty or a combination of these techniques.ConclusionEarly decompression in SCI patients remains a reasonable practice option and can be performed safely, but no specific evidence supports the use of laminectomy alone. There is emerging evidence that intended durotomy followed by extended meningoplasty may improve the neurological outcome in patients suffering from SCI when meta-traumatic edema is apparent. However, the lack of high-quality evidence and results support the need for further research.
| S-EPMC10543663 | biostudies-literature
Project description:Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG-sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.
| S-EPMC2895144 | biostudies-other
Project description:BackgroundMetastatic spinal cord compression (MSCC) treatment depends on life expectancies. Data regarding palliative decompression outcomes is scarce. We demonstrate that surgical timing has a significant impact on survival in MSCC patients treated with palliative decompression.MethodsEighty-nine consecutive MSCC patients at a tertiary referral medical center were enrolled between January 2012 and February 2016. Wide laminectomy was performed for tumors invading the vertebral body. Debulking surgery was done for tumors damaging the posterior column of the spine. Patient records were retrospectively analyzed.ResultsBetter survival was observed in patients with preoperative intact motor function (Group A, n = 37) than in those with motor deficit (Group B, n = 52, p = 0.0031). In Group B, survival was better in those who underwent surgery within 7 days of motor deficit onset than in those who underwent surgery 7 days after onset (p = 0.0444) and in postoperative ambulant patients than in nonambulant patients (p = 0.0120). In Group B, Frankel grade improved in patients who underwent surgery within 48 h than in those who underwent surgery after 48 h (p = 0.0992). Group A patients had a shorter hospital stay and higher revised Tokuhashi score than Group B patients. Overall survival was better in patients with a lower Tomita score (?5, p = 0.0012), higher revised Tokuhashi score (?9, p = 0.0009), better preoperative Frankel grade (p < 0.0001), and younger age (?55 years, p = 0.0179). There were no significant differences in age, sex, tumor type, involved vertebrae level, Tomita score, intraoperative blood loss, operation time, incidence of infection, and postoperative complications between groups.ConclusionWe can improve the survival of MSCC patients with palliative decompression before motor deficits occur. After motor deficit onset, survival can still be improved with surgery within 7 days. Overall survival was better in patients aged ?55 years.
| S-EPMC5747484 | biostudies-literature
Project description:We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.
| S-EPMC3378614 | biostudies-literature
Project description:The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.
| S-EPMC7873581 | biostudies-literature