title: The role of spreading depression in focal ischemia evaluated by diffusion mapping.
abstract: This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15-minute intervals, evaluated by continuous apparent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15-minute time epochs with a single SD episode (36.5 +/- 12.9 mm3, mean +/- SD) or multiple SD episodes (39.8 +/- 22.3) compared with those without SD (13.9 +/- 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after MCAO was significantly larger in the KCl group, with more total SDs (237.8 +/- 13.8) than the NaCl group (190.5 +/- 12.6) (p = 0.0001). This study demonstrates that ischemia-related and induced SDs increase significantly ischemic lesion volume in vivo, supporting the hypothesis for a causative role of SD in extending focal ischemic injury.
authors.affiliation: Department of Neurology, The Medical Center of Central Massachusetts-Memorial, Worcester 01605-2982, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.forename: L L
authors.initials: LL
authors.lastname: Latour
authors.forename: J E
authors.initials: JE
authors.lastname: Formato
authors.forename: R A
authors.initials: RA
authors.lastname: Carano
authors.forename: K G
authors.initials: KG
authors.lastname: Helmer
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: C H
authors.initials: CH
authors.lastname: Sotak
authors.forename: M
authors.initials: M
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume; D013997:Time Factors