Role of endothelial nitric oxide synthase in isoflurane conditioning-induced neurovascular protection in subarachnoid hemorrhage

Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J. Zipfel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

BACKGROUND: Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. METHODS AND RESULTS: Ten-to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic blanket. In a separate cohort, nitric oxide synthase was inhibited by a pan nitric oxide synthase inhibitor, L-nitroarginine methyl ester. Vasospasm measurement was assessed 72 hours after SAH and neurological function was assessed daily. Isoflurane-induced changes in the eNOS protein expression were measured. eNOS protein expression was significantly increased by isoflurane conditioning in naïve mice as well as mice subjected to SAH. Vasospasm of the middle cerebral artery and neurological deficits were evident following SAH versus sham surgery, both in wild-type mice and eNOS knockout mice. Isoflurane conditioning attenuated vasospasm and neurological deficits in wild-type mice. This delayed cerebral ischemia protection was lost in L-nitroarginine methyl ester-administered mice and eNOS knockout mice. CONCLUSIONS: Our data indicate isoflurane conditioning provides robust protection against SAH-induced vasospasm and neurological deficits, and that this delayed cerebral ischemia protection is critically mediated via isoflurane-induced augmentation of eNOS.

Original languageEnglish
Article numbere017477
JournalJournal of the American Heart Association
Volume9
Issue number20
DOIs
StatePublished - Oct 20 2020

Keywords

  • Aneurysmal subarachnoid hemorrhage
  • Delayed cerebral ischemia
  • Endothelial nitric oxide synthase
  • Isoflurane conditioning

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