title: Impaired CBF regulation and high CBF threshold contribute to the increased sensitivity of spontaneously hypertensive rats to cerebral ischemia.
abstract: The correlation between temporal changes of regional cerebral blood flow (rCBF) and the severity of transient ischemic stroke in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) was investigated using T2-, diffusion- and perfusion-weighted magnetic resonance imaging at six different time points: before and during 1h of unilateral middle cerebral artery occlusion (MCAO), 1h after reperfusion, and 1 day, 4 days and 7 days after MCAO. rCBF values were measured in both hemispheres, and the perfusion-deficient lesion (PDL) was defined as the area of the brain with a 57% or more reduction in basal CBF. Within the PDL, regions were further refined as ischemic core (rCBF=0-6 mL/100 g/min), ischemic penumbra (rCBF=6-15 mL/100 g/min) and benign oligemia (rCBF>15 mL/100 g/min). SHR and WKY had identical initial volume of the PDLs (WKY: 32.52 ± 4.08% vs. SHR: 33.95 ± 3.68%; P>0.05) and the maximum rCBF measured within those lesions (WKY: 38.20 ± 3.57 mL/100g/min vs. SHR: 38.46 ± 6.22 mL/100 g/min; P>0.05) during MCAO. However, in SHR virtually all of the PDL progressed to become the final ischemic lesion (33.02 ± 5.41%, P>0.05), while the final ischemic lesion volume of WKY (12.62 ± 9.19%) was significantly smaller than their original PDL (P<0.01) and similar to the ischemic core (13.13 ± 2.96%, P>0.05). The region with the lowest range of rCBF was positively correlated with the final ischemic lesion volume (r=0.716, P<0.01). Both during ischemia and after reperfusion, rCBF in either ipsilesional and contralesional brain hemispheres of SHR could not be restored to pre-ischemic levels, and remained lower than in WKY until up to 4 days after MCAO. The data suggest that impaired CBF regulation and relatively high CBF threshold for ischemia are strong contributors to the increased susceptibility of SHR to ischemic stroke.
authors.affiliation: Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Laboratory of Molecular Imaging and Translational Research, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
authors.forename: B-T
authors.initials: BT
authors.lastname: Kang
authors.affiliation: Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neuroscience and Behavioral Sciences, FMRP, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: R F
authors.initials: RF
authors.lastname: Leoni
authors.affiliation: Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: SilvaA@ninds.nih.gov.
authors.forename: A C
authors.initials: AC
authors.lastname: Silva
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012720:Severity of Illness Index; D013045:Species Specificity
keywords: arterial spin labeling; cerebral blood flow; ischemic stroke; magnetic resonance imaging; spontaneously hypertensive rats