title: Animal model for chronic massive rotator cuff tear: behavioural and histologic analysis.
abstract: OBJECTIVE
  Massive rotator cuff tears (MRCT) are usually chronic lesions that present associated degenerative changes of the myotendinous unit that have been implicated in limitations for surgical repair. In order to develop effective therapies, it is important to establish animal models that mimic the hallmarks of the injury itself. Therefore, in the present work, we aimed to (1) optimize a rodent animal model of MRCT that closely reproduces the fatty infiltration of the cuff muscles seen in humans and (2) describe the effects of unilateral or bilateral lesion in terms of histology and behaviour.
  
  
  METHODS
  Massive tear was defined as two rotator cuff tendons-supraspinatus and infraspinatus-section. Twenty-one Wistar rats were randomly assigned to four groups: bilateral lesion (five animals), right-sided unilateral lesion (five animals), left-sided unilateral lesion (five animals) and control (six animals). Behaviour was analyzed with open field and staircase test, 16 weeks after lesion. After that, animals were killed, and the supraspinatus and infraspinatus muscles were processed.
  
  
  RESULTS
  Histologic analysis revealed adipocytes, fatty infiltration and atrophy in the injured side with a greater consistency of these degenerative changes in the bilateral lesion group. Behaviour analysis revealed a significant functional impairment of the fine motor control of the forepaw analyzed in staircase test where the number of eaten pellets was significantly higher in sham animals (sham = 7 ± 5.0; left unilateral = 2.6 ± 3.0; right unilateral = 0 ± 0; and bilateral = 0 ± 0, p < 0.05). A trend to reach a lower level of steps, in more injured animals, was also observed (sham animals = 3 ± 1.6 > left unilateral = 2 ± 2.1 > right unilateral = 0.8 ± 1.3 > bilateral = 0.8 ± 1.1).
  
  
  CONCLUSIONS
  The present study has been able to establish an animal model that disclosed the hallmarks of MRCT. This can now be used as a valuable, cost-effective, pre-clinical instrument to assist in the development of advanced tissue engineered strategies. Moreover, this animal model overcomes some of the limitations of those that have been reported so far and thus represents a more reliable source for the assessment of future therapeutic strategies with potential clinical relevance.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal, nunosevivas@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Sevivas
authors.forename: S C
authors.initials: SC
authors.lastname: Serra
authors.forename: R
authors.initials: R
authors.lastname: Portugal
authors.forename: F G
authors.initials: FG
authors.lastname: Teixeira
authors.forename: M M
authors.initials: MM
authors.lastname: Carvalho
authors.forename: N
authors.initials: N
authors.lastname: Silva
authors.forename: J
authors.initials: J
authors.lastname: Espregueira-Mendes
authors.forename: N
authors.initials: N
authors.lastname: Sousa
authors.forename: A J
authors.initials: AJ
authors.lastname: Salgado
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017006:Rotator Cuff / Q000473:pathology* / Q000503:physiopathology; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000473:pathology* / Q000503:physiopathology