1. Academic Validation
  2. Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats

Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats

  • J Clin Neurosci. 2016 Dec;34:264-270. doi: 10.1016/j.jocn.2016.09.028.
Qiang Li 1 Yujie Chen 2 Xuan Zhang 2 Shilun Zuo 2 Hongfei Ge 2 Yanyan Chen 2 Xin Liu 2 John H Zhang 3 Huaizhen Ruan 4 Hua Feng 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
  • 3 Department of Anesthesiology, Neurosurgery and Physiology, Loma Linda University, Loma Linda, CA, USA.
  • 4 Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China. Electronic address: hzruan61@yahoo.com.
  • 5 Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: fenghua8888@vip.163.com.
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.

Keywords

Erk5; Scutellarin; Subarachnoid hemorrhage; Vasospasm; eNOS.

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