The changes of systemic immune responses during the neuroprotection induced by remote ischemic postconditioning against focal cerebral ischemia in mice

ABSTRACT

Objective: Remote limb ischemic postconditioning (RIPostC) protects the brain from damage induced by transient focal ischemia/reperfusion. However, the underlying mechanism remains unclear.

Methods: RIPostC induced by 10 min of occlusion and another 10 min releasing of blood flow for three cycles in the hind limbs was performed immediately after the reperfusion in a focal ischemia mice model. Neurological scores, immune cell population in the blood, spleen and lymph node, and inflammatory factors in the blood and brain were analyzed 2 days after the reperfusion.

Results: Our results demonstrate that RIPostC reduced cerebral injuries and improved neurological functions 2 days after reperfusion. RIPostC significantly inhibited the reduction in the percentage of CD4 T cells in the spleen and lymph node, CD8 T cells in the blood and lymph node, and natural killer T (NKT) cells in the spleen by flow cytometry analysis. RIPostC attenuated the increase of B cells and NK cells in the spleen and noninflammatory monocytes in the blood. The cytokine assay showed that RIPostC decreased the elevation of IL-10, IL-6, and TNF-α in the blood after ischemia. The quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) results indicated that the mRNA level of IL-4 in the brain increased in the middle cerebral artery occlusion mice after RIPostC treatment.

Conclusions: The present study indicates that there were significant changes of inflammatory responses during the neuroprotection induced by RIPostC in stroke mice.

KEYWORDS:

• Stroke
• middle cerebral artery occlusion
• remote ischemic postconditioning
• inflammatory response
• cytokine

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81701154), Tongzhou District Science and Technology Project (KJ2017CX039–02, KJ2018CX008–08) and the Tongzhou District Health Development Research and Special Project (TF-2017-PT-01–48).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81701154]; Tongzhou District Health Development Research and Special Project [TF-2017-PT-01–48]; Tongzhou District Science and Technology Project [KJ2017CX039–02, KJ2018CX008-08].

Notes on contributors

Cuiying Liu

Cuiying Liu obtained her Ph.D. in Neurobiology at Capital Medical University in 2012. Currently, she is a research assistant at the China–America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University. Her research interests include role of the noncoding mRNA and neuroinflammation after stroke.

Jian Yang

Jian Yang is a research apprentice at the China–America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University. His research interests focus on the mechanisms of remote precontioning against stroke.

Chencheng Zhang

Chencheng Zhangis a research associate at the China–America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University.

Xiaokun Geng

Xiaokun Gengis an associate professor of Neurology, Beijing Luhe Hospital, Capital Medical University. His main interests are the mechanism and drug protection against stroke.

Heng Zhao

Heng Zhaois an associate professor (Research) of Department of Neurosurgery, Stanford University. His group is working toward finding the methods, mechanism to reduce the injury after stroke.