Dataset Information

Sirt3 deficiency impairs neurovascular recovery in ischemic stroke.

ABSTRACT:

Aims

Sirt3 is one member of the NAD⁺ -dependent protein deacetylase family and plays crucial roles in diverse aspects of mammalian biological function. Then the role of Sirt3 on ischemia stroke is unknown.

Methods

To examine the effect of Sirt3 on ischemic stroke, we performed transient middle cerebral artery occlusion (tMCAO) in adult male Sirt3 knockout (KO) and wild-type (WT) mice.

Results

The level of Sirt3 in infarct region is decreased after ischemic stroke. In addition, we found that Sirt3 KO mice showed worse neurobehavioral outcome compared with WT mice, accompanied by decreased neurogenesis and angiogenesis as shown by the reduction in number of DCX⁺ /BrdU⁺ cells, NeuN⁺ /BrdU⁺ cells, and CD31⁺ /BrdU⁺ cells in the perifocal region during recovery phase after ischemic stroke. Furthermore, Sirt3 deficiency reduced the activation of vascular endothelial growth factor (VEGF), AKT, and extracellular signal-regulated kinases (ERK) signaling pathways.

Conclusion

Our results indicated that Sirt3 is beneficial to neurovascular and functional recovery following chronic ischemic stroke.

SUBMITTER: Yang X

PROVIDER: S-EPMC6490148 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Sirt3 deficiency impairs neurovascular recovery in ischemic stroke.

Yang Xiao X Geng Ke-Yi KY Zhang Yan-Shuang YS Zhang Jin-Fan JF Yang Ke K Shao Jia-Xiang JX Xia Wei-Liang WL

CNS neuroscience & therapeutics 20180518 9

<h4>Aims</h4>Sirt3 is one member of the NAD<sup>+</sup> -dependent protein deacetylase family and plays crucial roles in diverse aspects of mammalian biological function. Then the role of Sirt3 on ischemia stroke is unknown.<h4>Methods</h4>To examine the effect of Sirt3 on ischemic stroke, we performed transient middle cerebral artery occlusion (tMCAO) in adult male Sirt3 knockout (KO) and wild-type (WT) mice.<h4>Results</h4>The level of Sirt3 in infarct region is decreased after ischemic stroke ...[more]

PMID: 29777578

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Project description:Background: Innate immune response to neuronal death is one of the key events of the pathogenesis of ischemic brain injury. Interleukin-1 receptor-associated kinase (IRAK)-M, encoded by gene Irak3, negatively regulates toll-like receptor signaling by interacting with the MyD88-IRAK-4-IRAK-1 complex and blocking the phosphorylation and dissociation of IRAK-1. Its function in the ischemic stroke is unknown. Objective: This study aims to investigate whether IRAK-M deficiency could exacerbate neuroinflammation and neurovascular injuries during cerebral ischemia and reperfusion. Methods: Male C57BL/6 mice and Irak3 knockout mice were subjected to 45 min of middle cerebral artery occlusion and 4 or 24 h of reperfusion. Transcription of Irak3 gene was evaluated by quantitative real-time PCR (qRT-PCR). Then, infarct volume, neurological score, brain water content, and Evans blue leakage were compared between knock-out and wild-type mice after reperfusion. Through the observation of gross brain specimen after cerebral ischemia, the incidence of hemorrhage transformation was compared between KO and WT mice. To explore underlying signaling pathways involved in IRAK-M deficiency, major proinflammatory cytokines and NF-κB signaling were measured by qRT-PCR and Western blot. Results: The expression of IRAK-M peaked at 1 h after reperfusion, and then gradually decreased within the first 24 h, which was abolished by blocking the expression of hypoxia induced factor 1α. IRAK-M deficiency increased infarct volume, brain edema, the incidence of hemorrhage transformation, and the permeability of blood-brain barrier. In addition, the NF-κB-mediated expressions of proinflammatory cytokines and the activation of microglia in the ipsilateral brain from knock-out mice were much higher than those in wild-type littermates. Conclusion: IRAK-M deletion exacerbates neurovascular damages which are related to the pronounced activation of NF-κB signaling and neuroinflammatory responses during cerebral ischemia-reperfusion in mice. Our study indicates that IRAK-M has neuroprotective effect and has potential to facilitate the development of new pharmaceuticals that reduce neurovascular complications.

Dataset Information

Sirt3 deficiency impairs neurovascular recovery in ischemic stroke.

Aims

Methods

Results

Conclusion

Publications

Sirt3 deficiency impairs neurovascular recovery in ischemic stroke.

Similar Datasets

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