Dataset Information

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

ABSTRACT: Despite the variety of experimental models of spinal cord injury (SCI) currently used, the model of the ventral compression cord injury, which is commonly seen in humans, is very limited. Ventral balloon compression injury reflects the common anatomical mechanism of a human lesion and has the advantage of grading the injury severity by controlling the inflated volume of the balloon. In this study, ventral compression of the SCI was performed by the anterior epidural placement of the balloon of a 2F Fogarty's catheter, via laminectomy, at the level of T10. The balloon was rapidly inflated with 10 or 15 ?L of saline and rested in situ for 5 min. The severity of the lesion was assessed by behavioral and immunohistochemical tests. Compression with the volume of 15 ?L resulted in severe motor and sensory deficits represented by the complete inability to move across a horizontal ladder, a final Basso, Beattie and Bresnahan (BBB) score of 7.4 and a decreased withdrawal time in the plantar test (11.6 s). Histology and immunohistochemistry revealed a significant loss of white and gray matter with a loss of motoneuron, and an increased size of astrogliosis. An inflation volume of 10 ?L resulted in a mild transient deficit. There are no other balloon compression models of ventral spinal cord injury. This study provided and validated a novel, easily replicable model of the ventral compression SCI, introduced by an inflated balloon of Fogarty´s catheter. For a severe incomplete deficit, an inflated volume should be maintained at 15 ?L.

SUBMITTER: Krupa P

PROVIDER: S-EPMC7694490 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

Krupa Petr P Stepankova Katerina K Kwok Jessica Cf JC Fawcett James W JW Cimermanova Veronika V Jendelova Pavla P Machova Urdzikova Lucia L

Biomedicines 20201105 11

Despite the variety of experimental models of spinal cord injury (SCI) currently used, the model of the ventral compression cord injury, which is commonly seen in humans, is very limited. Ventral balloon compression injury reflects the common anatomical mechanism of a human lesion and has the advantage of grading the injury severity by controlling the inflated volume of the balloon. In this study, ventral compression of the SCI was performed by the anterior epidural placement of the balloon of a ...[more]

PMID: 33167447

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Project description:OBJECTIVE:Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS:To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS:High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION:EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

Project description:BackgroundMetastatic epidural spinal cord compression (MESCC) is a devastating complication of advanced cancer. A deep learning (DL) model for automated MESCC classification on MRI could aid earlier diagnosis and referral.PurposeTo develop a DL model for automated classification of MESCC on MRI.Materials and methodsPatients with known MESCC diagnosed on MRI between September 2007 and September 2017 were eligible. MRI studies with instrumentation, suboptimal image quality, and non-thoracic regions were excluded. Axial T2-weighted images were utilized. The internal dataset split was 82% and 18% for training/validation and test sets, respectively. External testing was also performed. Internal training/validation data were labeled using the Bilsky MESCC classification by a musculoskeletal radiologist (10-year experience) and a neuroradiologist (5-year experience). These labels were used to train a DL model utilizing a prototypical convolutional neural network. Internal and external test sets were labeled by the musculoskeletal radiologist as the reference standard. For assessment of DL model performance and interobserver variability, test sets were labeled independently by the neuroradiologist (5-year experience), a spine surgeon (5-year experience), and a radiation oncologist (11-year experience). Inter-rater agreement (Gwet's kappa) and sensitivity/specificity were calculated.ResultsOverall, 215 MRI spine studies were analyzed [164 patients, mean age = 62 ± 12(SD)] with 177 (82%) for training/validation and 38 (18%) for internal testing. For internal testing, the DL model and specialists all showed almost perfect agreement (kappas = 0.92-0.98, p < 0.001) for dichotomous Bilsky classification (low versus high grade) compared to the reference standard. Similar performance was seen for external testing on a set of 32 MRI spines with the DL model and specialists all showing almost perfect agreement (kappas = 0.94-0.95, p < 0.001) compared to the reference standard.ConclusionA DL model showed comparable agreement to a subspecialist radiologist and clinical specialists for the classification of malignant epidural spinal cord compression and could optimize earlier diagnosis and surgical referral.

Project description:Simple Summary Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy, and early diagnosis is important to prevent irreversible neurological injury. MRI is the mainstay of diagnosis for MESCC, but it is expensive, and routine screening of asymptomatic patients is not feasible. Staging CT studies are performed routinely as part of the cancer diagnosis and represent an opportunity for earlier diagnosis and treatment planning. In this study, we trained deep learning models for automatic MESCC classification on staging CT studies using spine MRI and manual radiologist labels as the reference standard. On a test set, the DL models showed almost-perfect interobserver agreement for the classification of CT spine images into normal, low, and high-grade MESCC, with kappas ranging from 0.873–0.911 (p < 0.001). The DL models (lowest κ = 0.873, 95% CI 0.858–0.887) also showed superior interobserver agreement compared to two radiologists, including a specialist (κ = 0.820, 95% CI 0.803–0.837) and general radiologist (κ = 0.726, 95% CI 0.706–0.747), both p < 0.001. Abstract Background: Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy. Deep learning (DL) models for automatic MESCC classification on staging CT were developed to aid earlier diagnosis. Methods: This retrospective study included 444 CT staging studies from 185 patients with suspected MESCC who underwent MRI spine studies within 60 days of the CT studies. The DL model training/validation dataset consisted of 316/358 (88%) and the test set of 42/358 (12%) CT studies. Training/validation and test datasets were labeled in consensus by two subspecialized radiologists (6 and 11-years-experience) using the MRI studies as the reference standard. Test sets were labeled by the developed DL models and four radiologists (2–7 years of experience) for comparison. Results: DL models showed almost-perfect interobserver agreement for classification of CT spine images into normal, low, and high-grade MESCC, with kappas ranging from 0.873–0.911 (p < 0.001). The DL models (lowest κ = 0.873, 95% CI 0.858–0.887) also showed superior interobserver agreement compared to two of the four radiologists for three-class classification, including a specialist (κ = 0.820, 95% CI 0.803–0.837) and general radiologist (κ = 0.726, 95% CI 0.706–0.747), both p < 0.001. Conclusion: DL models for the MESCC classification on a CT showed comparable to superior interobserver agreement to radiologists and could be used to aid earlier diagnosis.

Project description:Intramedullary spinal cord tumors are a rare and understudied cancer with poor treatment options and prognosis. Our prior study used a combination of PDGF-B, HRAS, and p53 knockdown to induce the development of high-grade glioma in the spinal cords of minipigs. In this study, we evaluate the ability of each vector alone and combinations of vectors to produce high-grade spinal cord gliomas. Eight groups of rats (n = 8/group) underwent thoracolumbar laminectomy and injection of lentiviral vector in the lateral white matter of the spinal cord. Each group received a different combination of lentiviral vectors expressing PDGF-B, a constitutively active HRAS mutant, or shRNA targeting p53, or a control vector. All animals were monitored once per week for clinical deficits for 98 days. Tissues were harvested and analyzed using hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining. Rats injected with PDGF-B+HRAS+sh-p53 (triple cocktail) exhibited statistically significant declines in all behavioral measures (Basso Beattie Bresnahan scoring, Tarlov scoring, weight, and survival rate) over time when compared to the control. Histologically, all groups except the control and those injected with sh-p53 displayed the development of tumors at the injection site, although there were differences in the rate of tumor growth and the histopathological features of the lesions between groups. Examination of immunohistochemistry revealed rats receiving triple cocktail displayed the largest and most significant increase in the Ki67 proliferation index and GFAP positivity than any other group. PDGF-B+HRAS also displayed a significant increase in the Ki67 proliferation index. Rats receiving PDGF-B alone and PDGF-B+ sh-p53 displayed more a significant increase in SOX2-positive staining than in any other group. We found that different vector combinations produced differing high-grade glioma models in rodents. The combination of all three vectors produced a model of high-grade glioma more efficiently and aggressively with respect to behavioral, physiological, and histological characteristics than the rest of the vector combinations. Thus, the present rat model of spinal cord glioma may potentially be used to evaluate therapeutic strategies in the future.

Dataset Information

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

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New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

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