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

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...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 2022-07, Vol.42 (7), p.1210-1223
Main Authors: Clarke, Julian V, Brier, Lindsey M, Rahn, Rachel M, Diwan, Deepti, Yuan, Jane Y, Bice, Annie R, Imai, Shin-ichiro, Vellimana, Ananth K, Culver, Joseph P, Zipfel, Gregory J
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Mice
Mice, Inbred C57BL
Original
Resveratrol - pharmacology
Sirtuin 1 - metabolism
Subarachnoid Hemorrhage - complications
Subarachnoid Hemorrhage - drug therapy
Subarachnoid Hemorrhage - metabolism
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Summary: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.
ISSN:0271-678X
1559-7016
DOI:10.1177/0271678X221079902