title: Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents.
abstract: Spontaneous spreading depolarizations are frequent after various forms of human brain injury such as ischemic or hemorrhagic stroke and trauma, and worsen the outcome. We have recently shown that supply-demand mismatch transients trigger spreading depolarizations in ischemic stroke. Here, we examined the mechanisms triggering recurrent spreading depolarization events for many days after subarachnoid hemorrhage. Despite large volumes of subarachnoid hemorrhage induced by cisternal injection of fresh arterial blood in rodents, electrophysiological recordings did not detect a single spreading depolarization for up to 72 h after subarachnoid hemorrhage. Cortical susceptibility to spreading depolarization, measured by direct electrical stimulation or topical KCl application, was suppressed after subarachnoid hemorrhage. Focal cerebral ischemia experimentally induced after subarachnoid hemorrhage revealed a biphasic change in the propensity to develop peri-infarct spreading depolarizations. Frequency of peri-infarct spreading depolarizations decreased at 12 h, increased at 72 h and normalized at 7 days after subarachnoid hemorrhage compared with sham controls. However, ischemic tissue and neurological outcomes were significantly worse after subarachnoid hemorrhage even when peri-infarct spreading depolarization frequency was reduced. Laser speckle flowmetry implicated cerebrovascular hemodynamic mechanisms worsening the outcome. Altogether, our data suggest that cerebral ischemia is required for spreading depolarizations to be triggered after subarachnoid hemorrhage, which then creates a vicious cycle leading to the delayed cerebral ischemia syndrome.
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.|2 Department of Neurosurgery, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Oka
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.|3 Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Chung
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yuzawa
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Shih-Pin
authors.initials: SP
authors.lastname: Chen
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Yahya B
authors.initials: YB
authors.lastname: Atalay
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.|4 Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, Boston, USA.
authors.forename: Ala
authors.initials: A
authors.lastname: Nozari
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Kristen Park
authors.initials: KP
authors.lastname: Hopson
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: 1 Department of Radiology, Massachusetts General Hospital, Charlestown, USA.|3 Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*
keywords: Subarachnoid hemorrhage; delayed cerebral ischemia; middle cerebral artery occlusion; peri-infarct depolarization; spreading depolarization