Abstract
Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model. M/Ms-specific Sirt3 knockout Sirt3f/f; CX3CR1-Cre (Sirt3 cKO) mouse was used to evaluate the role of Sirt3 on RSV treatment. Neuronal function and hematoma volume were assessed to indicate brain damage. The pro-inflammatory marker (CD16) and cytokine (TNF) were measured to evaluate the inflammatory effects. Our results showed that RSV treatment alleviates neurological deficits, reduces cell death, and increases hematoma clearance on day 7 after ICH. In addition, RSV effectively suppressed CD16+ M/Ms activation and decreased TNF release. In Sirt3 cKO mice, the protective effects of RSV were abolished, indicating the potential mechanism of RSV was partially due to Sirt3 signaling activation. Therefore, RSV could be a promising candidate and therapeutic agent for ICH and Sirt3 could be a potential target to inhibit inflammation.
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Data Availability
The datasets used and/or analyzed during the current study are available in the Additional file 1: Data Supplement except for these listed in the article. Only the representative images from H&E and IHC/IF stains are available in the article.
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Funding
This study was supported by the National Natural Science Foundation of China (No.81901186, No.82171458, No.82101374, and No.81974188).
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SHD and XFJ were the conceivers and designers of this study. They directed and oversaw the development and implementation of studies in this work. PL and XL directed and advised the writing and editing of the manuscript. JDS, PC and EWY designed and conducted all the experiments and wrote the manuscript. YF, HCZ and YFY collected all the samples and performed the behavioral tests. LZ assisted in analyzing the data.
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Sun, J., Pu, C., Yang, E. et al. Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice. Cell Mol Neurobiol 43, 2871–2882 (2023). https://doi.org/10.1007/s10571-023-01325-9
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DOI: https://doi.org/10.1007/s10571-023-01325-9