Dataset Information

Refinement of the spinal cord injury rat model and validation of its applicability as a model for memory loss and chronic pain.

ABSTRACT:

Background

Laminectomy produces trauma in spinal cord injury (SCI) animal models resulting in impinging artefacts and welfare issues. Mechanizing laminectomy using a dental burr assisted (DBA) technique to reduce the impact of conventionally performed laminectomy on animal welfare without any alterations in the outcome of the model was previously demonstrated. However, further validation was necessary to establish it as an alternative in developing SCI rats as a model of chronic pain and memory loss.

Novel method

DBA technique was employed to perform laminectomy at T10-T11 vertebrae in rats undergoing contusion SCI as a model of chronic pain and memory loss. In a 56-day study, 24 female Wistar rats (Crl: WI) were assigned randomly to four equal groups: conventionally laminectomised, DBA laminectomised, conventionally laminectomised with SCI and DBA laminectomised with SCI.

Results

The study revealed DBA technique to cause less surgical bleeding (p = 0.001), lower Rat Grimace Scale (p = 0.0006); resulted in better body weight changes (p = 0.0002 on Day 7 and p = 0.0108 on Day 28) and dark phase activity (p = .0.0014 on Day 1; p = 0.0422 on Day 56). Different techniques did not differ in Basso Beattie Bresnahan score, novel object recognition, mechanical allodynia, number of surviving neurons and the area of vacuolation- indicating that the new method doesn't affect the validity of the model.

Comparison with existing methods

In comparison with the conventional technique, motorised laminectomy can be a valid tool that evokes lesser pain and ensures higher well-being in rats modelled for chronic pain and memory loss.

Conclusions

The intended outcome from the model is not influenced by techniques whereas the DBA-technique is a refined alternative to the conventional method in achieving better welfare in SCI studies.

SUBMITTER: Harikrishnan VS

PROVIDER: S-EPMC8278431 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Refinement of the spinal cord injury rat model and validation of its applicability as a model for memory loss and chronic pain.

Harikrishnan V S VS Palekkodan Hamza H Fasaludeen Ansar A Krishnan Lissy K LK Abelson Klas S P KSP

Heliyon 20210707 7

<h4>Background</h4>Laminectomy produces trauma in spinal cord injury (SCI) animal models resulting in impinging artefacts and welfare issues. Mechanizing laminectomy using a dental burr assisted (DBA) technique to reduce the impact of conventionally performed laminectomy on animal welfare without any alterations in the outcome of the model was previously demonstrated. However, further validation was necessary to establish it as an alternative in developing SCI rats as a model of chronic pain and ...[more]

PMID: 34286145

Similar Datasets

Project description:BackgroundCancer-induced bone pain (CIBP) is a moderate to severe pain and seriously affects patients' quality of life. Spinal cord plays critical roles in pain generation and maintenance. Identifying differentially expressed proteins (DEPs) in spinal cord is essential to elucidate the mechanisms of cancer pain.MethodsCIBP rat model was established by the intratibial inoculation of MRMT-1 cells. Positron emission tomography (PET) scan and transmission electron microscopy (TEM) were used to measure the stats of spinal cord in rats. Label free Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) were used to analyze the whole proteins from the lumbar spinal cord. Differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and verified using Western blot and immunofluorescence assay.ResultsIn the current study, CIBP rats exhibited bone damage, spontaneous pain, mechanical hyperalgesia, and impaired motor ability. In spinal cord, an hypermetabolism and functional abnormality were revealed on CIBP rats. An increase of synaptic vesicles density in active zone and a disruption of mitochondrial structure in spinal cord of CIBP rats were observed. Meanwhile, 422 DEPs, consisting of 167 up-regulated and 255 down-regulated proteins, were identified among total 1539 proteins. GO enrichment analysis indicated that the DEPs were mainly involved in catabolic process, synaptic function, and enzymic activity. KEGG pathway enrichment analysis indicated a series of pathways, including nervous system disease, hormonal signaling pathways and amino acid metabolism, were involved. Expression change of synaptic and mitochondrial related protein, such as complexin 1 (CPLX1), synaptosomal-associated protein 25 (SNAP25), synaptotagmin 1 (SYT1), aldehyde dehydrogenase isoform 1B1 (ALDH1B1), Glycine amidinotransferase (GATM) and NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), were further validated using immunofluorescence and Western blot analysis.ConclusionThis study provides valuable information for understanding the mechanisms of CIBP, and supplies potential therapeutic targets for cancer pain.

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

Refinement of the spinal cord injury rat model and validation of its applicability as a model for memory loss and chronic pain.

Background

Novel method

Results

Comparison with existing methods

Conclusions

Publications

Refinement of the spinal cord injury rat model and validation of its applicability as a model for memory loss and chronic pain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets