title: Hemodynamics and metabolism in stroke-prone spontaneously hypertensive rats before manifestation of brain infarcts.
abstract: Genomic screening of hybrids from stroke-prone (SHR-SP) and stroke-resistant spontaneously hypertensive rats (SHR) identified a STR1 locus on the rat chromosome 1, which correlates with the susceptibility to cerebral stroke but not with hypertension. The authors examined whether this genetic abnormality is associated with hemodynamic or metabolic alterations in the brain that can be detected before the manifestation of brain infarction. Starting at 6 weeks of age, SHR-SP were fed with a salt-rich diet to accelerate arterial hypertension. At the age of 12 weeks, animals developed functional symptoms and were age-matched with symptom-negative SHR-SP to differentiate between presymptomatic and postsymptomatic changes. Brains were investigated by multiparametric imaging comprising quantitative double-tracer autoradiography of CBF and cerebral protein synthesis (CPS); bioluminescence imaging of regional ATP, glucose, and lactate content; and umbelliferone fluoroscopic imaging of tissue pH. None of the animals exhibited focal hemodynamic or biochemical abnormalities. In symptom-negative SHR-SP, global CBF was 1.1+/-0.3 mL x g(-1) x min(-1), cortical CPS was 10.1+/-3.1 nmol x g(-1) x min(-1), and cortical ATP, glucose, lactate, and pH levels were in the normal range. In SHR-SP with functional symptoms, ATP, glucose, and lactate levels also were normal, but tissue pH exhibited periventricular alkalosis, CBF was significantly reduced to 0.7+/-0.2 mL x g(-1) x min(-1) (P < 0.001), and cortical CPS was significantly reduced to 6.7+/-2.1 nmol x g(-1) x min(-1) (P < 0.001). The decline in brain perfusion of SHR-SP correlated significantly with both the severity of functional deficits and the decline of protein synthesis. Our observations demonstrate that SHR-SP had already developed functional symptoms before the manifestation of overt brain infarcts and that the symptoms are initiated by a decline in global CBF and cortical CPS. Genetic abnormalities in SHR-SP are associated with a diffuse vascular process that results in global decompensation of blood flow well before the onset of focal brain infarction.
authors.affiliation: Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Köln, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Mies
authors.forename: D
authors.initials: D
authors.lastname: Hermann
authors.forename: U
authors.initials: U
authors.lastname: Ganten
authors.forename: K A
authors.initials: KA
authors.lastname: Hossmann
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000378:metabolism* / Q000503:physiopathology*; D004032:Diet; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR