SIRT1 mediates hypoxic postconditioning- and resveratrol-induced protection against functional connectivity deficits after subarachnoid hemorrhage

Julian V. Clarke, Lindsey M. Brier, Rachel M. Rahn, Deepti Diwan, Jane Y. Yuan, Annie R. Bice, Shin Ichiro Imai, Ananth K. Vellimana, Joseph P. Culver, Gregory J. Zipfel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SAH induce deficits in FC; 2) Does exposure to hypoxic conditioning provide protection against these FC deficits and, if so, is this neurovascular protection SIRT1-mediated; and 3) does treatment with the SIRT1 activator resveratrol alone provide protection against these FC deficits? Cranial windows were adhered on skull-intact mice that were then subjected to either sham or SAH surgery and either left untreated or treated with hypoxic post-conditioning (with or without EX527) or resveratrol for 3 days. Mice were imaged 3 days post-SAH/sham surgery, temporally aligned with the onset of major SAH sequela in mice. Here we show that the endovascular perforation model of SAH induces global and network-specific deficits in FC by day 3, corresponding with the time frame of DCI in mice. Hypoxic conditioning provides SIRT1-mediated protection against these network-specific FC deficits post-SAH, as does treatment with resveratrol. Conditioning-based strategies provide multifaceted neurovascular protection in experimental SAH.

Original languageEnglish
Pages (from-to)1210-1223
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume42
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • Functional connectivity
  • delayed cerebral ischemia
  • experimental subarachnoid hemorrhage
  • optical intrinsic signal
  • sirtuins

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