Optimized cervical spinal cord perfusion MRI after traumatic injury in the rat.
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ABSTRACT:
SUBMITTER: Meyer BP
PROVIDER: S-EPMC8327111 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background/objectivesWe recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPPopt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPPopt can be predicted using clinical factors instead of ISP monitoring.MethodsSixty-four TSCI patients, grades A-C (American spinal injuries association Impairment Scale, AIS), were analyzed. For 24 h after surgery, we monitored ISP and SCPP and computed SCPPopt (SCPP that optimizes pressure reactivity). We studied how well 28 factors correlate with mean ISP or SCPPopt including 7 patient-related, 3 injury-related, 6 management-related, and 12 preoperative MRI-related factors.ResultsAll patients underwent surgery to restore normal spinal alignment within 72 h of injury. Fifty-one percentage had U-shaped sPRx versus SCPP curves, thus allowing SCPPopt to be computed. Thirteen percentage, all AIS grade A or B, had no U-shaped sPRx versus SCPP curves. Thirty-six percentage (22/64) had U-shaped sPRx versus SCPP curves, but the SCPP did not reach the minimum of the curve, and thus, an exact SCPPopt could not be calculated. In total 5/28 factors were associated with lower ISP: older age, excess alcohol consumption, nonconus medullaris injury, expansion duroplasty, and less intraoperative bleeding. In a multivariate logistic regression model, these 5 factors predicted ISP as normal or high with 73% accuracy. Only 2/28 factors correlated with lower SCPPopt: higher mean ISP and conus medullaris injury. In an ordinal multivariate logistic regression model, these 2 factors predicted SCPPopt as low, medium-low, medium-high, or high with only 42% accuracy. No MRI factors correlated with ISP or SCPPopt.ConclusionsElevated ISP can be predicted by clinical factors. Modifiable factors that may lower ISP are: reducing surgical bleeding and performing expansion duroplasty. No factors accurately predict SCPPopt; thus, invasive monitoring remains the only way to estimate SCPPopt.
| S-EPMC6420421 | biostudies-literature
Project description:Study Design Retrospective comparative study. Objective A narrow spinal canal is an important risk factor for predicting a spinal cord injury (SCI); however, the radiologic parameters have not been fully established. The authors conducted a comparative study to forecast SCI risk by determining a predictive spinal canal diameter (SCD) cutoff value from magnetic resonance image (MRI) in the Korean population. Methods On T2-weighted MRI of the cervical spine, the SCD at the pedicle (SCDpedicle) and the intervertebral disk level (SCDdisk) were measured in patients with SCI without spinal instability and in healthy subjects. Additionally, the vertebral body diameter (Dvertebral body) and intervertebral disk diameter (Dintervertebral disk) were measured, and the two ratios (SCDpedicle to Dvertebral body and SCDdisk to Dintervertebral disk) were calculated. In the SCI group, the extent of high signal intensity on the T2-weighted midsagittal MRI was determined. Results The data obtained from 20 patients in the SCI group (18 men, mean age 61.35 years) and 65 individuals in the control group (47 men, mean age 57.05 years) was compared. All the parameters including the SCD and the calculated ratios were significantly smaller in the SCI group than in the control group. Among them, the area under the receiver operating curve (AUC) value for the SCDdisk-to-Dintervertebral disk ratio at C2-C3, with a cutoff ratio value of 0.59, provided the greatest positive predictive value. A low SCDdisk-to-Dintervertebral disk ratio at C4-C5 and the presence of >40 mm of high signal intensity on the MRI were related with the presence of complete SCI. Conclusion Because the C2-C3 level is relatively wide compared with the subaxial cervical spine, a small ratio at C2-C3 provided the greatest positive predictive value in SCI. Complete SCI is associated with a small SCDdisk-to-Dintervertebral disk ratio at C4-C5 and with extensive high signal intensity on MRI.
| S-EPMC4516744 | biostudies-other
Project description:Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore- and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.
| S-EPMC4186801 | biostudies-other
Project description:Study designSystematic review update.ObjectivesInterventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI.MethodsWe searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence.ResultsFrom 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment.ConclusionsThis update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting.
| S-EPMC10964891 | biostudies-literature
Project description:The aim of the present study was to investigate the key genes associated with traumatic spinal cord injuries (TSCI). The dataset GSE52763 was downloaded from the Gene Expression Omnibus, for which lumbar spinal cord samples were obtained from rats at 1 and 3 weeks following contusive spinal cord injury and 1 week subsequent to a sham laminectomy, and used to identify differentially expressed genes (DEGs). Functional enrichment analysis, co‑expression analysis and transcription factor (TF) identification were performed for DEGs common to the 1 and 3 week injury samples. In total, 234 upregulated and 51 downregulated DEGs were common to the 1 and 3 week injury samples. The upregulated DEGs were significantly enriched in Gene Ontology terms concerning immunity (e.g. Itgal and Ccl2) and certain pathways, including natural killer cell mediated cytotoxicity [e.g. Ras‑related C3 botulinum toxin substrate 2 (Rac2) and TYRO protein tyrosine kinase binding protein (Tyrobp)]. The downregulated DEGs were highly enriched in female gonad development [e.g. progesterone receptor (Pgr)], and the steroid biosynthesis pathway. A total of 139 genes had co‑expression associations and the majority of them were upregulated genes. The upregulated co‑expressed genes were predominantly enriched in biological regulation, including TGFB induced factor homeobox 1 (Tgif1) and Rac2. The downregulated co‑expressed genes were enriched in anatomical structure development (e.g. Dnm3). A total of 92 co‑expressed genes composed the protein‑protein interaction network. Additionally, 9 TFs (e.g. Pgr and Tgif1) were identified from the DEGs. It was hypothesized that the genes including Tgif1, Rac2, Tyrobp, and Pgr may be closely associated with TSCI.
| S-EPMC5364992 | biostudies-literature
Project description:Recent studies showed that RNA N6-methyladenosine (m6A) plays an important role in neurological diseases. We used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) technology to generate the m6A modification map after traumatic spinal cord injury (TSCI). A total of 2,609 differential m6A peaks were identified after TSCI. Our RNA sequencing results after TSCI showed 4,206 genes with significantly altered expression. Cross-link analysis of m6A sequencing results and RNA sequencing results showed that 141 hyper-methylated genes were upregulated, 53 hyper-methylated genes were downregulated, 57 hypo-methylated genes were upregulated, and 197 hypo-methylated genes were downregulated. Among these, the important inflammatory response factor Tlr4 and the important member of the neurotrophin family Ngf were both upregulated and hyper-methylated after TSCI. This study provides that in the future, the epigenetic modifications of the genes could be used as an indicator of TSCI.
| S-EPMC9189298 | biostudies-literature
Project description:Traumatic spinal cord injury (SCI) is associated with a lifetime of disability stemming from loss of motor, sensory, and autonomic functions; these losses, along with increased comorbid sequelae, negatively impact health outcomes and quality of life. Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI. After an SCI, the enzyme, Rho, is activated by growth-inhibitory factors and regulates events that culminate in collapse of the neuronal growth cone, failure of axonal regeneration, and, ultimately, failure of motor and functional recovery. Inhibition of Rho activation is a potential treatment for injuries such as traumatic SCI. VX-210, an investigational agent, inhibits Rho. When administered extradurally after decompression (corpectomy or laminectomy) and stabilization surgery in a phase 1/2a study, VX-210 was well tolerated. Here, we describe the design of the SPRING trial, a multicenter, phase 2b/3, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of VX-210 (NCT02669849). A subset of patients with acute traumatic cervical SCI is currently being enrolled in the United States and Canada. Medical, neurological, and functional changes are evaluated at 6 weeks and at 3, 6, and 12 months after VX-210 administration. Efficacy will be assessed by the primary outcome measure, change in upper extremity motor score at 6 months post-treatment, and by secondary outcomes that include question-based and task-based evaluations of functional recovery.
| S-EPMC5908415 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Acute markers of spinal cord injury are essential for both diagnostic and prognostic purposes. The goal of this study was to assess the relationship between early MR imaging biomarkers after acute cervical spinal cord injury and to evaluate their predictive validity of neurologic impairment. MATERIALS AND METHODS:We performed a retrospective cohort study of 95 patients with acute spinal cord injury and preoperative MR imaging within 24 hours of injury. The American Spinal Injury Association Impairment Scale was used as our primary outcome measure to define neurologic impairment. We assessed several MR imaging features of injury, including axial grade (Brain and Spinal Injury Center score), sagittal grade, length of injury, maximum canal compromise, and maximum spinal cord compression. Data-driven nonlinear principal component analysis was followed by correlation and optimal-scaled multiple variable regression to predict neurologic impairment. RESULTS:Nonlinear principal component analysis identified 2 clusters of MR imaging variables related to 1) measures of intrinsic cord signal abnormality and 2) measures of extrinsic cord compression. Neurologic impairment was best accounted for by MR imaging measures of intrinsic cord signal abnormality, with axial grade representing the most accurate predictor of short-term impairment, even when correcting for surgical decompression and degree of cord compression. CONCLUSIONS:This study demonstrates the utility of applying nonlinear principal component analysis for defining the relationship between MR imaging biomarkers in a complex clinical syndrome of cervical spinal cord injury. Of the assessed imaging biomarkers, the intrinsic measures of cord signal abnormality were most predictive of neurologic impairment in acute spinal cord injury, highlighting the value of axial T2 MR imaging.
| S-EPMC5671488 | biostudies-literature
Project description:Traumatic spinal cord injury (SCI) results in impaired neurologic function that for many individuals is permanent and significantly impacts health, function, quality of life, and life expectancy. Many efforts have been taken to develop effective treatments for SCI; nevertheless, proven therapies targeting neurologic regeneration and functional recovery have been limited. Existing therapeutic approaches, including early surgery, strict blood pressure control, and consideration of treatment with steroids, remain debated and largely focus on mitigating secondary injury after the primary trauma has occurred. Today, there is more research being performed in SCI than ever before. Current clinical trials are exploring pharmacologic, cell-based, physiologic, and rehabilitation approaches to reduce secondary injury and also overcome barriers to neurorecovery. In the future, it is likely that tailored treatments combining many of these strategies will offer significant benefits for persons with SCI. This article aims to review key past, current and emerging neurologic and rehabilitation therapeutic approaches for adults with traumatic SCI.
| S-EPMC6095794 | biostudies-literature
Project description:Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.
| S-EPMC8848590 | biostudies-literature