title: Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage.
abstract: Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T2-weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233 mm(3)) than in the no-SD group (29 ± 54 mm(3)) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Arend M
authors.initials: AM
authors.lastname: Hamming
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke J H
authors.initials: MJH
authors.lastname: Wermer
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Umesh Rudrapatna
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Lanier
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hine J A
authors.initials: HJA
authors.lastname: van Os
authors.affiliation: Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Walter M
authors.initials: WM
authors.lastname: van den Bergh
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: van der Toorn
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arn M J M
authors.initials: AMJM
authors.lastname: van den Maagdenberg
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Stowe
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Centre Utrecht, Utrecht, The Netherlands r.m.dijkhuizen@umcutrecht.nl.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*
keywords: Subarachnoid hemorrhage; animal models; brain imaging; magnetic resonance; spreading depression