title: Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage.
abstract: Although there have been several investigations regarding acute brain injury after subarachnoid hemorrhage (SAH), the pathological conditions of severe SAH are unclear. In this study, we pursued the characteristics of cerebrovascular injury in the hyperacute phase after experimentally induced severe SAH. Twenty-three male Sprague-Dawley rats were subjected to sham or SAH operation using the endovascular perforation method and were evaluated for brain edema, blood-brain barrier (BBB) permeability, and arterial endothelial cell injury at 5 min after SAH (experiment 1). Next, animals were examined for functional and morphological changes of cerebral artery for 30 min after an acetazolamide injection administered 5 min after SAH (experiment 2). In experiment 1, while cerebral blood flow (CBF) was reduced, brain edema was not observed in SAH-operated rats. BBB permeability detected by immunoglobulin G extravasation was observed in the optic tract and was accompanied by the upregulation of phosphorylated extracellular signal-regulated kinase (ERK)-positive astrocytes. In addition, the number of phosphorylated ERK-positive endothelial cell in the distal middle cerebral artery (MCA) was significantly increased by SAH. In experiment 2, CBF in non-lethal SAH rats was reduced, and no response to acetazolamide was detected. Conversely, CBF in lethal SAH increased due to acetazolamide, although the value of CBF was low. Furthermore, there was significant narrowing of the MCA in SAH-operated rats. The findings suggest that the optic tract and the cerebral artery are the most vulnerable areas regarding cerebrovascular injury in a hyperacute phase after severe SAH and that they are associated with fatal outcomes.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan. fpmhasse@yahoo.co.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-shi, Mie-ken, 5148507, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Uekawa
authors.affiliation: Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan.
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001812:Blood-Brain Barrier / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D065866:Optic Tract / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
chemical_list: D048052:Mitogen-Activated Protein Kinase 3
keywords: Cerebral blood flow; Hyperacute phase; Middle cerebral artery; Optic tract; Phosphorylated extracellular signal-regulated kinase; Severe subarachnoid hemorrhage