title: Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats.
abstract: Angiographic vasospasm, especially in the early phases (<72h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague-Dawley rats. Then, the underlying mechanism of the anti-vasospasm effect of SCU was investigated using a modified Garcia scale, India ink angiography, cross-sectional area analysis, immunohistochemistry staining and western blot. SCU (50μM, 100mg/kg) alleviated angiographic vasospasm and improved neurological function 48h after SAH and enhanced the expression of endothelial nitric oxide synthase (eNOS) at the intima of cerebral arteries. In addition, SCU upregulated the expression of phosphorylated extracellular-regulated kinase 5 (p-Erk5) and Kruppel-like factor 2 (KLF2) at 48h after SAH. However, the effects of SCU were reversed by the Erk5 inhibitor XMD8-92. Our results indicate that SCU could attenuate vasospasm and neurological deficits via modulating the Erk5-KLF2-eNOS pathway after SAH, which may provide an experimental basis for the clinical use of SCU treatment in SAH patients.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China; Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Shilun
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Neurosurgery and Physiology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China. Electronic address: hzruan61@yahoo.com.
authors.forename: Huaizhen
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: fenghua8888@vip.163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D049919:Erigeron; D005965:Glucuronates / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology
chemical_list: D004365:Drugs, Chinese Herbal; D005965:Glucuronates; C484876:scutellarin; D047310:Apigenin; D052250:Nitric Oxide Synthase Type III; D048054:Mitogen-Activated Protein Kinase 7
keywords: Erk5; Scutellarin; Subarachnoid hemorrhage; Vasospasm; eNOS