-Original-

Responses of Immune Organs after Cerebral Ischemic Stroke

Chengbo Tan^1-3, Zifeng Wang³, Miao Zheng⁴, Songji Zhao², Hideo Shichinohe^3,5 and Kiyohiro Houkin³

¹Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
²Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, Fukushima, Japan
³Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
⁴Department of Dermatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
⁵Division of Clinical Research Administration, Hokkaido University Hospital, Sapporo, Japan

Background: Stroke is a leading cause of death and disability worldwide. Recently, secondary damage to the brain has been hypothesized as a key aggravating element in the ischemic cascade. However, the interaction between cerebral infarction and immune organs is not fully understood. In this study, we investigated changes in rat brain, spleen, thymus, mesenteric lymph node, and liver at 3, 7, and 13 days after transient middle cerebral artery occlusion (tMCAO) by immunohistochemistry.
Methods: Rat models of stroke were made by tMCAO. Functional assessment was performed at 3 h and 1, 3, 5, 7, 9, 11, and 13 days after MCAO. Rat organs were harvested for 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry.
Results: The number of CD8α⁺ T cells decreased in spleen, thymus, mesenteric lymph node, and liver and increased in brain. Numbers of Iba1⁺ and CD68⁺ macrophages decreased in spleen, thymus, and mesenteric lymph node and increased in brain and liver. Ki67⁺ cells exhibited the same characteristics as macrophages, and increased numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive apoptotic cells were present in spleen, mesenteric lymph node, liver, and brain.
Conclusions: The present results indicate that stroke is a systemic disease that, in addition to affecting the brain, also induces responses in immune organs. These results suggest that systemic treatment might be a good strategy for clinical stroke care.

J Nippon Med Sch 2021; 88: 228-237

Keywords
cerebral ischemic stroke, inflammation, immune organ response, histological analysis

Correspondence to
Songji Zhao, MD, PhD, Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, 1 Hikariga-oka, Fukushima City, Fukushima 960-1295, Japan
zhao-s@fmu.ac.jp

Received, September 8, 2019
Accepted, July 31, 2020