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Veterinary journal (London, England : 1997)2012; 195(3); 305-312; doi: 10.1016/j.tvjl.2012.07.003

Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses.

Abstract: Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6-48h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.
Publication Date: 2012-08-09 PubMed ID: 22884985DOI: 10.1016/j.tvjl.2012.07.003Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article is about an investigation into the early, pre-clinical stage of equine laminitis, a disease in horses induced excessively by insulin. The research aimed to explore both qualitatively and quantitatively the effect of high insulin levels on the lamellar structure in horse hooves as the disease progresses, even before the clinical symptoms appear.

Objective of the Study

  • The objective of this research was to study the initial, developmental phase of insulin-induced laminitis in horses, a disease condition characterized by inflammation within the structures of the hoof.
  • The researchers aimed to study the alterations, or ‘lesions’, on the lamellar structure of the horse’s hooves caused by excessive insulin levels, over a 48-hour period from the commencement of the hyperinsulinaemic condition.

Methodology

  • The study involved histological and histomorphometrical analyses of the lamellar pathology.
  • The parameters tracked for changes included lamellar length and width, cell proliferation and death, basement membrane (BM) pathology, and infiltration of white blood cells or leucocytes.
  • The researchers analyzed archived tissue from control horses and those which had acute laminitis which had been stimulated by insulin, and used nuclear immuno labelling for TPX2 to further evaluate cellular proliferative activity.

Findings

  • Within six hours of hyperinsulinaemia, the disease began with a decrease in the width of secondary epidermal lamellae (SEL) and an increase in the cellular death in these regions.
  • Later on, within 24 to 48 hours, there was an increase in cellular proliferation in the SELs, small numbers of leucocytes began to infiltrate the dermis, and damage to the basement membrane (BM) started to occur.
  • Some changes, such as narrowing of the SELs, were observed to progressively worsen over the examined period.
  • The changes in cell pathology appeared before the leucocyte infiltration and BM damage, suggesting these alterations may be secondary or downstream events in hyperinsulinaemic laminitis.

Conclusion

  • The study’s findings have deepened the understanding of the pre-clinical, developmental stage of insulin-induced laminitis in horses, revealing how cellular changes occur before any signs of inflammation or BM damage. Hence, these changes might serve as early indicators of the disease in future.

Cite This Article

APA
de Laat MA, Patterson-Kane JC, Pollitt CC, Sillence MN, McGowan CM. (2012). Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses. Vet J, 195(3), 305-312. https://doi.org/10.1016/j.tvjl.2012.07.003

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 195
Issue: 3
Pages: 305-312
PII: S1090-0233(12)00306-1

Researcher Affiliations

de Laat, Melody A
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. melody.de_Laat@okstate.edu
Patterson-Kane, Janet C
    Pollitt, Christopher C
      Sillence, Martin N
        McGowan, Catherine M

          MeSH Terms

          • Animals
          • Cell Death
          • Epidermal Cells
          • Foot Diseases / chemically induced
          • Foot Diseases / pathology
          • Foot Diseases / veterinary
          • Horse Diseases / chemically induced
          • Horse Diseases / pathology
          • Horses
          • Inflammation / chemically induced
          • Inflammation / pathology
          • Inflammation / veterinary
          • Insulin / toxicity
          • Male
          • Mitosis

          Citations

          This article has been cited 8 times.
          1. Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW. Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model.. J Vet Intern Med 2020 Jul;34(4):1606-1613.
            doi: 10.1111/jvim.15835pubmed: 32583504google scholar: lookup
          2. de Laat MA, Spence RJ, Sillence MN, Pollitt CC. An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis.. PLoS One 2019;14(12):e0225843.
            doi: 10.1371/journal.pone.0225843pubmed: 31805097google scholar: lookup
          3. Pollard D, Wylie CE, Verheyen KLP, Newton JR. Identification of modifiable factors associated with owner-reported equine laminitis in Britain using a web-based cohort study approach.. BMC Vet Res 2019 Feb 12;15(1):59.
            doi: 10.1186/s12917-019-1798-8pubmed: 30755193google scholar: lookup
          4. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019 Mar;33(2):335-349.
            doi: 10.1111/jvim.15423pubmed: 30724412google scholar: lookup
          5. Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA. Equine glucagon-like peptide-1 receptor physiology.. PeerJ 2018;6:e4316.
            doi: 10.7717/peerj.4316pubmed: 29404215google scholar: lookup
          6. Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J. Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model.. J Vet Intern Med 2018 Jan;32(1):450-458.
            doi: 10.1111/jvim.15027pubmed: 29282770google scholar: lookup
          7. Giles SL, Nicol CJ, Rands SA, Harris PA. Assessing the seasonal prevalence and risk factors for nuchal crest adiposity in domestic horses and ponies using the Cresty Neck Score.. BMC Vet Res 2015 Jan 31;11:13.
            doi: 10.1186/s12917-015-0327-7pubmed: 25636243google scholar: lookup
          8. Gauff FC, Patan-Zugaj B, Licka TF. Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses.. Am J Vet Res 2014 Apr;75(4):367-74.
            doi: 10.2460/ajvr.75.4.367pubmed: 24669922google scholar: lookup