Dataset Information

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam.

ABSTRACT:

Introduction

Treatments for patients with cauda equina injury are limited.

Methods

In this study, we first used retrograde labeling to determine the relative contributions of cauda equina motor neurons to intrinsic and extrinsic rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to bridge the proximal and distal stumps with either a type I collagen scaffold coated in laminin (CL) or a collagen-laminin scaffold that was also seeded with Schwann cells (CLSC). Regeneration was assessed by way of serial retrograde labeling.

Results

After accounting for the axonal contributions to intrinsic vs. extrinsic tail muscles, we noted a higher degree of double labeling in the CLSC group (58.0 ± 39.6%) as compared with the CL group (27.8 ± 16.0%; P = 0.02), but not the control group (33.5 ± 18.2%; P = 0.10).

Discussion

Our findings demonstrate the feasibility of using CLSCs in cauda equina injury repair. Muscle Nerve 57: E78-E84, 2018.

SUBMITTER: Mackenzie SJ

PROVIDER: S-EPMC5722669 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam.

Mackenzie Samuel J SJ Yi Juneyoung L JL Singla Amit A Russell Thomas M TM Osterhout Donna J DJ Calancie Blair B

Muscle & nerve 20170813 1

<h4>Introduction</h4>Treatments for patients with cauda equina injury are limited.<h4>Methods</h4>In this study, we first used retrograde labeling to determine the relative contributions of cauda equina motor neurons to intrinsic and extrinsic rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to bridge the proximal and distal stumps with either a type I collagen scaffold coated in laminin (CL) or a collagen-laminin scaffold that was also seeded with Schwann cells (CL ...[more]

PMID: 28746726

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Project description:IntroductionPersistent neuroinflammatory response after cauda equina injury (CEI) lowers nociceptor firing thresholds, accompanied by pathological pain and decreasing extremity dysfunction. Histone deacetylation has been considered a key regulator of immunity, inflammation, and neurological dysfunction. Our previous study suggested that valproic acid (VPA), a histone deacetylase inhibitor, exhibited neuroprotective effects in rat models of CEI, although the underlying mechanism remains elusive.MethodsThe cauda equina compression surgery was performed to establish the CEI model. The Basso, Beattie, Bresnahan score, and the von Frey filament test were carried out to measure the animal behavior. Immunofluorescence staining of myelin basic protein and GPX4 was carried out. In addition, transmission electron microscope analysis was used to assess the effect of VPA on the morphological changes of mitochondria. RNA-sequencing was conducted to clarify the underlying mechanism of VPA on CEI protection.ResultsIn this current study, we revealed that the expression level of HDAC1 and HDAC2 was elevated after cauda equina compression model but was reversed by VPA treatment. Meanwhile, HDAC2 knockdown resulted in the improvement of motor functions and pathologic pain, similar to treatment with VPA. Histology analysis also showed that knockdown of histone deacetylase (HDAC)-2, but not HDAC1, remarkably alleviated cauda equina injury and demyelinating lesions. The potential mechanism may be related to lowering oxidative stress and inflammatory response in the injured region. Notably, the transcriptome sequencing indicated that the therapeutic effect of VPA may depend on HDAC2-mediated ferroptosis. Ferroptosis-related genes were analyzed in vivo and DRG cells further validated the reliability of RNA-sequencing results, suggesting HDAC2-H4K12ac axis participated in epigenetic modulation of ferroptosis-related genes.ConclusionHDAC2 is critically involved in the ferroptosis and neuroinflammation in cauda equina injury, and VPA ameliorated cauda equina injury by suppressing HDAC2-mediated ferroptosis.

Project description:IntroductionCauda Equina Syndrome (CES) can cause persisting life-changing dysfunction. There is scarce literature regarding the long-term assessment of CES symptoms, and rarer still is the impact of these symptoms on mental wellbeing investigated. This study assessed the long-term patient reported mental wellbeing outcomes of post-operative CES patients.MethodsPatients who underwent surgery for CES between August 2013 and November 2014 were identified using an ethically approved database. They then completed validated questionnaires over the telephone assessing their mental and physical functioning (Short-Form 12 Questionnaire), generating the Physical Component Summary (PCS) and Mental Component Summary (MCS). Bladder, bowel and sexual function were also assessed using validated questionnaires. MCS scores were compared to both the Scottish mean and previously published cut-offs indicating patients at risk of depression. Correlations of MCS with bladder, bowel, sexual and physical dysfunction were examined and multifactorial regression to predict MCS from these variables analysed. Independent t-tests assessed the mean difference in MCS between patients presenting with incomplete CES (CES-I) and CES with retention (CES-R) and between those with radiologically confirmed and impending CES.ResultsForty-six participants with a mean follow-up time of 43 months completed the study. The mean (±SD) MCS was 49 (±11.8) with 22% demonstrating poor mental health related quality of life in comparison to the Scottish mean. Overall, 37% had scores consistent with being at risk for depression with in the last 30 days, and 45% within the last 12 months. MCS was significantly correlated with Urinary Symptoms Profile (USP) score (-0.608), NBDS score (-0.556), ASEX score (-0.349) and PCS score (0.413) with worse bladder, bowel, sexual and physical dysfunction associated with worse MCS score. Multifactorial regression analysis demonstrated both urinary (USP score p = 0.031) and bowel function (NBDS score p = 0.009) to be significant predictive variables of mental health related quality of life. There were no significant mean differences in MCS between those presenting with CES-I and CES-R or those with radiologically complete and impending CES.DiscussionThis study demonstrates a high frequency of being at risk for depression in patients with CES and identifies outcome measures (physical, sexual and more so bladder and bowel dysfunction) associated with poorer mental wellbeing. Our large cohort and long follow-up highlight that CES patients should be considered at risk of depression, and the need to consider mental health outcomes following CES surgery.

Dataset Information

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam.

Introduction

Methods

Results

Discussion

Publications

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam.

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