title: Brain remodelling following endothelin-1 induced stroke in conscious rats.
abstract: The extent of stroke damage in patients affects the range of subsequent pathophysiological responses that influence recovery. Here we investigate the effect of lesion size on development of new blood vessels as well as inflammation and scar formation and cellular responses within the subventricular zone (SVZ) following transient focal ischemia in rats (n = 34). Endothelin-1-induced stroke resulted in neurological deficits detected between 1 and 7 days (P<0.001), but significant recovery was observed beyond this time. MCID image analysis revealed varying degrees of damage in the ipsilateral cortex and striatum with infarct volumes ranging from 0.76-77 mm3 after 14 days, where larger infarct volumes correlated with greater functional deficits up to 7 days (r = 0.53, P<0.05). Point counting of blood vessels within consistent sample regions revealed that increased vessel numbers correlated significantly with larger infarct volumes 14 days post-stroke in the core cortical infarct (r = 0.81, P<0.0001), core striatal infarct (r = 0.91, P<0.005) and surrounding border zones (r = 0.66, P<0.005; and r = 0.73, P<0.05). Cell proliferation within the SVZ also increased with infarct size (P<0.01) with a greater number of Nestin/GFAP positive cells observed extending towards the border zone in rats with larger infarcts. Lesion size correlated with both increased microglia and astrocyte activation, with severely diffuse astrocyte transition, the formation of the glial scar being more pronounced in rats with larger infarcts. Thus stroke severity affects cell proliferation within the SVZ in response to injury, which may ultimately make a further contribution to glial scar formation, an important factor to consider when developing treatment strategies that promote neurogenesis.
authors.affiliation: Department of Surgery, St Vincent's Campus, University of Melbourne, Victoria, Australia.
authors.forename: Hima C S
authors.initials: HC
authors.lastname: Abeysinghe
authors.affiliation: Neurotrauma Research team, Department of Medicine, St Vincent's Campus, University of Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia.
authors.forename: Laita
authors.initials: L
authors.lastname: Bokhari
authors.affiliation: Cytoprotection Pharmacology Program, Centre for Eye Research, The Royal Eye and Ear Hospital Melbourne, Victoria, Australia; Department of Opthamology, Faculty of Medicine, University of Melbourne, Victoria, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Neurotrauma Research team, Department of Medicine, St Vincent's Campus, University of Melbourne, Victoria, Australia.
authors.forename: Carli L
authors.initials: CL
authors.lastname: Roulston
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D020520:Brain Infarction / Q000150:complications; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003243:Consciousness; D019332:Endothelin-1 / Q000009:adverse effects*; D020547:Lateral Ventricles / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D019332:Endothelin-1