title: Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat.
abstract: Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm2 calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4128, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Dawson
authors.forename: C A
authors.initials: CA
authors.lastname: Ruetzler
authors.forename: J M
authors.initials: JM
authors.lastname: Hallenbeck
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003911:Dextrans; D005070:Evans Blue; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion; D013997:Time Factors
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D005070:Evans Blue; D016650:Fluorescein-5-isothiocyanate