AIMS: The spontaneously hypertensive stroke-prone rat (SHRSP) is a potential animal model of human lacunar stroke, but there is little information on SHRSP small vessel pathology, especially in young rats. We investigated the structural changes that occur in cortical and subcortical vessels and adjacent tissue in SHRSP before, during and after the onset of hypertension. METHODS: We examined brains from SHRSP and Wistar Kyoto rats (WKY) at 5, 16 and 21 weeks of age. Structural changes in small arterioles and adjacent tissue were studied using antibodies to investigate different components of the neurovascular unit. We quantified staining in three standard regions, at two coronal levels. RESULTS: Immunostaining for claudin-5, a marker of endothelial tight junctions, was reduced in SHRSP at all ages compared to age-matched WKY controls. Smooth muscle actin, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 were increased in SHRSP vs. WKY by 16 weeks. Additionally, 21-week-old WKY and SHRSP rats fed a high-salt diet showed differences in claudin-5, glial fibrillary acidic protein and matrix metalloproteinase 9 staining compared to those fed a normal diet. CONCLUSION: Endothelial tight junction alterations of SHRSP rats from the earliest ages point towards increased susceptibility to blood-brain barrier dysfunction and stroke, which is exacerbated by salt loading. Salt loading may also damage the neurovascular unit in WKY controls.
AIMS: The spontaneously hypertensive stroke-prone rat (SHRSP) is a potential animal model of humanlacunar stroke, but there is little information on SHRSP small vessel pathology, especially in young rats. We investigated the structural changes that occur in cortical and subcortical vessels and adjacent tissue in SHRSP before, during and after the onset of hypertension. METHODS: We examined brains from SHRSP and Wistar Kyoto rats (WKY) at 5, 16 and 21 weeks of age. Structural changes in small arterioles and adjacent tissue were studied using antibodies to investigate different components of the neurovascular unit. We quantified staining in three standard regions, at two coronal levels. RESULTS: Immunostaining for claudin-5, a marker of endothelial tight junctions, was reduced in SHRSP at all ages compared to age-matched WKY controls. Smooth muscle actin, glial fibrillary acidic protein and ionizedcalcium-binding adaptor molecule 1 were increased in SHRSP vs. WKY by 16 weeks. Additionally, 21-week-old WKY and SHRSP rats fed a high-salt diet showed differences in claudin-5, glial fibrillary acidic protein and matrix metalloproteinase 9 staining compared to those fed a normal diet. CONCLUSION: Endothelial tight junction alterations of SHRSP rats from the earliest ages point towards increased susceptibility to blood-brain barrier dysfunction and stroke, which is exacerbated by salt loading. Salt loading may also damage the neurovascular unit in WKY controls.
Authors: Paul R Krafft; Emma L Bailey; Tim Lekic; William B Rolland; Orhan Altay; Jiping Tang; Joanna M Wardlaw; John H Zhang; Cathie L M Sudlow Journal: Int J Stroke Date: 2012-07 Impact factor: 5.266
Authors: James W Nelson; Sharon C Phillips; Bhanu P Ganesh; Joseph F Petrosino; David J Durgan; Robert M Bryan Journal: FASEB J Date: 2021-02 Impact factor: 5.191
Authors: Victoria E O'Collins; Geoffrey A Donnan; Malcolm R Macleod; David W Howells Journal: J Cereb Blood Flow Metab Date: 2013-06-05 Impact factor: 6.200
Authors: Philip R Holland; James L Searcy; Natalia Salvadores; Gillian Scullion; Guiquan Chen; Greig Lawson; Fiona Scott; Mark E Bastin; Masafumi Ihara; Rajesh Kalaria; Emma R Wood; Colin Smith; Joanna M Wardlaw; Karen Horsburgh Journal: J Cereb Blood Flow Metab Date: 2015-02-11 Impact factor: 6.200
Authors: Karen Horsburgh; Joanna M Wardlaw; Tom van Agtmael; Stuart M Allan; Mike L J Ashford; Philip M Bath; Rosalind Brown; Jason Berwick; M Zameel Cader; Roxana O Carare; John B Davis; Jessica Duncombe; Tracy D Farr; Jill H Fowler; Jozien Goense; Alessandra Granata; Catherine N Hall; Atticus H Hainsworth; Adam Harvey; Cheryl A Hawkes; Anne Joutel; Rajesh N Kalaria; Patrick G Kehoe; Catherine B Lawrence; Andy Lockhart; Seth Love; Malcolm R Macleod; I Mhairi Macrae; Hugh S Markus; Chris McCabe; Barry W McColl; Paul J Meakin; Alyson Miller; Maiken Nedergaard; Michael O'Sullivan; Terry J Quinn; Rikesh Rajani; Lisa M Saksida; Colin Smith; Kenneth J Smith; Rhian M Touyz; Rebecca C Trueman; Tao Wang; Anna Williams; Steven C R Williams; Lorraine M Work Journal: Clin Sci (Lond) Date: 2018-04-30 Impact factor: 6.124
Authors: Jian Guan; Allen C Clermont; Loc-Duyen Pham; Tuna Ustunkaya; Alexey S Revenko; A Robert MacLeod; Edward P Feener; Fabrício Simão Journal: Transl Stroke Res Date: 2021-07-09 Impact factor: 6.829