Sodium Tanshinone IIA Sulfonate Protects Against Cerebral Ischemia-reperfusion Injury by Inhibiting Autophagy and Inflammation.

Abstract

Sodium tanshinone IIA sulfonate (STS) can protect against brain damage induced by stroke. However, the neural protection mechanism of STS remains unclear. We investigated whether STS performs its protective function by suppressing autophagy and inflammatory activity during brain injury. We established a transient middle cerebral artery occlusion and reperfusion (MCAO/R) model by blocking the left middle cerebral artery with a thread inserted through the internal carotid artery for 1 h, followed by reperfusion for 48 h either with or without STS and the autophagy inhibitor 3-methyladenine (3-MA). Neuroprotective effects were determined by evaluating infarction, brain edema, and neurological deficits. The numbers of microglia-derived macrophages, monocyte-derived microglia, T cells, and B cells in the brains were measured, based on the surface marker analyses of CD45, CD11b, B220, CD3, and CD4 using fluorescence-assisted cell sorting. STS (10, 20, 40 mg/kg) was able to significantly reduce infarct volumes, improve neurological deficits, and reduce brain water contents. STS treatment reduced neuroinflammation, as assessed by the infiltration of macrophages and neutrophils, corresponding with reduced numbers of macrophages, T cells, and B cells in ischemia/reperfusion (I/R) brains. In addition, STS treatment also attenuated the upregulation of autophagy associated proteins, such as LC3-II, Beclin-1 and Sirt 6, which was induced by MCAO. These results demonstrated that STS can provide remarkable protection against ischemic stroke, possibly via the inhibition of autophagy and inflammatory activity.

• Authors: Lei Wang, Xiaoxing Xiong, Xu Zhang, Yingze Ye, Zhihong Jian, Wenwei Gao, Lijuan Gu
• Journal: Neuroscience (Neuroscience) Vol. 441 Pg. 46-57 (08 10 2020) ISSN: 1873-7544 [Electronic] United States
• PMID: 32505745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Phenanthrenes
• tanshinone II A sodium sulfonate

Topics

• Animals
• Autophagy
• Brain Ischemia
• Disease Models, Animal
• Infarction, Middle Cerebral Artery
• Inflammation (drug therapy)
• Neuroprotective Agents (pharmacology)
• Phenanthrenes
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, prevention & control)