title: Peri-infarct flow transients predict outcome in rat focal brain ischemia.
abstract: Spreading depolarizations are accompanied by transient changes in cerebral blood flow (CBF). In a post hoc analysis of previously studied control rats we analyzed CBF time courses after middle cerebral artery occlusion in the rat in order to test whether intra-ischemic flow, reperfusion, and different parameters of peri-infarct flow transients (PIFTs) (amplitude, number) can predict outcome. Sprague-Dawley rats anesthetized with either halothane (n=23) or isoflurane (n=32) underwent 90-min filament occlusion of the middle cerebral artery followed by 72 h of reperfusion. The infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Relative CBF changes were monitored by laser Doppler flowmetry at 4-5 mm lateral, and 1-2mm posterior to Bregma. An additional filament occlusion study (n=12) was performed to validate that PIFTs were coupled to direct current shifts of spreading depolarization. The PIFT-direct current shift study revealed that every PIFT was associated with a negative direct current shift typical of spreading depolarization. Post-hoc analysis showed that the number of PIFTs, especially with the combination of intra-ischemic level of flow, can predict the development of cortical infarcts. These findings show that PIFTs can serve as an early biomarker in predicting outcome in preclinical animal studies.
authors.affiliation: Department of Neurology, University of Pennsylvania, 415 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6063, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lückl
authors.forename: J P
authors.initials: JP
authors.lastname: Dreier
authors.forename: T
authors.initials: T
authors.lastname: Szabados
authors.forename: D
authors.initials: D
authors.lastname: Wiesenthal
authors.forename: F
authors.initials: F
authors.lastname: Bari
authors.forename: J H
authors.initials: JH
authors.lastname: Greenberg
mesh_terms: D000758:Anesthesia; D000769:Anesthesia, Inhalation; D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000097:blood; D002544:Cerebral Infarction / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004396:Coloring Agents; D006221:Halothane; D006863:Hydrogen-Ion Concentration; D007530:Isoflurane; D017078:Laser-Doppler Flowmetry; D016015:Logistic Models; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles; D016896:Treatment Outcome
chemical_list: D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D002245:Carbon Dioxide; D007530:Isoflurane; C022616:thiazolyl blue; D010100:Oxygen; D006221:Halothane