Dataset Information

Sex Differences in Rat Intervertebral Disc Structure and Function Following Annular Puncture Injury.

ABSTRACT: STUDY DESIGN:A rat puncture injury intervertebral disc (IVD) degeneration model with structural, biomechanical, and histological analyses. OBJECTIVE:To determine if males and females have distinct responses in the IVD after injury. SUMMARY OF BACKGROUND DATA:Low back pain (LBP) and spinal impairments are more common in women than men. However, sex differences in IVD response to injury have been underexplored, particularly in animal models where sex differences can be measured without gender confounds. METHODS:Forty-eight male and female Sprague Dawley rats underwent sham, single annular puncture with tumor necrosis factor ? (TNF?) injection (1×), or triple annular puncture with TNF? injection (3×) surgery. Six weeks after surgery, lumbar IVDs were assessed by radiologic IVD height, spinal motion segment biomechanical testing, histological degeneration grading, second harmonic generation (SHG) imaging, and immunofluorescence for fibronectin and ?-smooth muscle actin. RESULTS:Annular puncture injuries significantly increased degenerative grade and IVD height loss for males and females, but females had increased degeneration grade particularly in the annulus fibrosus (AF). Despite IVD height loss, biomechanical properties were largely unaffected by injury at 6 weeks. However, biomechanical measures sensitive to outer AF differed by sex after 3× injury-male IVDs had greater torsional stiffness, torque range, and viscoelastic creep responses. SHG intensity of outer AF was reduced after injury only in female IVDs, suggesting sex differences in collagen remodeling. Both males and females exhibited decreased cellularity and increased fibronectin expression at injury sites. CONCLUSION:IVD injury results in distinct degeneration and functional healing responses between males and females. The subtle sex differences identified in this animal model suggest differences in response to IVD injury that might explain some of the variance observed in human LBP, and demonstrate the need to better understand differences in male and female IVD degeneration patterns and pain pathogenesis. LEVEL OF EVIDENCE:N/A.

SUBMITTER: Mosley GE

PROVIDER: S-EPMC6722021 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Sex Differences in Rat Intervertebral Disc Structure and Function Following Annular Puncture Injury.

Mosley Grace E GE Hoy Robert C RC Nasser Philip P Kaseta Timothy T Lai Alon A Evashwick-Rogler Thomas W TW Lee Michael M Iatridis James C JC

Spine 20190901 18

<h4>Study design</h4>A rat puncture injury intervertebral disc (IVD) degeneration model with structural, biomechanical, and histological analyses.<h4>Objective</h4>To determine if males and females have distinct responses in the IVD after injury.<h4>Summary of background data</h4>Low back pain (LBP) and spinal impairments are more common in women than men. However, sex differences in IVD response to injury have been underexplored, particularly in animal models where sex differences can be measur ...[more]

PMID: 30973506

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Project description:BackgroundIntervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).MethodsCaudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague-Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242.ResultsFindings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs.ConclusionsOur findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.

Project description:BackgroundVertebral endplate sclerosis and facet osteoarthritis have been documented in animals and humans. However, it is unclear how these adjacent pathologies engage in crosstalk with the intervertebral disc. This study sought to elucidate this crosstalk by assessing each compartment individually in response to acute disc injury.MethodsEleven New Zealand White rabbits underwent annular disc puncture using a 16G or 21G needle. At 4 and 10 weeks, individual compartments of the motion segment were analyzed. Discs underwent T 1 relaxation mapping with MRI contrast agent gadodiamide as well T 2 mapping. Both discs and facets underwent mechanical testing via vertebra-disc-vertebra tension-compression creep testing and indentation testing, respectively. Endplate bone density was quantified via μCT. Discs and facets were sectioned and stained for histology scoring.ResultsIntervertebral discs became more degenerative with increasing needle diameter and time post-puncture. Bone density also increased in endplates adjacent to both 21G and 16G punctured discs leading to reduced gadodiamide transport at 10 weeks. The facet joints, however, did not follow this same trend. Facets adjacent to 16G punctured discs were less degenerative than facets adjacent to 21G punctured discs at 10 weeks. 16G facets were more degenerative at 4 weeks than at 10, suggesting the cartilage had recovered. The formation of severe disc osteophytes in 16G punctured discs between 4 and 10 weeks likely offloaded the facet cartilage, leading to the recovery observed.ConclusionsOverall, this study supports that degeneration spans the whole spinal motion segment following disc injury. Vertebral endplate thickening occurred in response to disc injury, which limited the diffusion of small molecules into the disc. This work also suggests that altered disc mechanics can induce facet degeneration, and that extreme bony remodeling adjacent to the disc may promote facet cartilage recovery through offloading of the articular cartilage.

Project description:Background: There is heterogeneity in neurosensory alterations following mild traumatic brain injury. Commonly assessed neurosensory symptoms following head injury include symptom reports and measures of oculomotor impairment, auditory changes, and vestibular impairment. Hypothesis/Purpose: Neurosensory alterations are prevalent acutely following mild traumatic brain injury secondary to blunt head trauma during collegiate varsity sports and may vary by sex and sport. Study Design: Retrospective study of a large collegiate athletic database. Methods: Analyses were performed using an established single University dataset of 177 male and female collegiate varsity athletes who were diagnosed with concussion/mild traumatic brain injury between September 2013 and October 2019. Descriptive and comparative analyses were performed on individual and grouped acute concussion assessments pertaining to neurosensory alterations obtained within 72 h of injury using components of the Sports Concussion Assessment Tool Version 5 and Vestibular/Ocular-Motor Screening. Results: Females had significantly more abnormal smooth pursuit (p-value: 0.045), convergence (p-value: 0.031), and visual motion sensitivity tests results (p-value: 0.023) than males. There were no differences in neurosensory alterations when grouped by overall auditory, vestibular, or oculomotor impairments. The majority of sports-related concussions occurred during football (50, 28.25%), wrestling (21, 11.86%), water polo (15, 8.47%), and basketball (14, 7.91%). Abnormal vestibular assessments were high in these top four sports categories, but statistically significant differences in overall auditory, vestibular, or oculomotor impairments were not reached by individual sport. However, water polo players had higher abnormal individual assessments related to balance reports on the sideline (60.00%, p-value: 0.045) and in the clinic setting (57.14%, p-value: 0.038) as compared to all other sports. Conclusion: While neurosensory alterations are prevalent in both male and female athletes acutely post-concussion, females have a higher incidence of abnormalities in smooth pursuit, convergence, and visual motion sensitivity and may benefit from early rehabilitation.

Dataset Information

Sex Differences in Rat Intervertebral Disc Structure and Function Following Annular Puncture Injury.

Publications

Sex Differences in Rat Intervertebral Disc Structure and Function Following Annular Puncture Injury.

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