ORIGINAL RESEARCH article

Front. Physiol.

Sec. Exercise Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1580283

Exercise Preconditioning Alleviates Photothrombotic Ischemic Stroke in Mice by Orchestrating Neutrophils

Provisionally accepted
Tae Yeon  KimTae Yeon Kim1Yun Seo  ChoYun Seo Cho1Jaeyeon  ParkJaeyeon Park1Songwon  WooSongwon Woo1Kihoon  YukKihoon Yuk1Dong Heon  YiDong Heon Yi1In cheol  JeongIn cheol Jeong2Jin Pyeong  JeonJin Pyeong Jeon2Yoe-Sik  BaeYoe-Sik Bae3mclee@cha.ac.kr  Leemclee@cha.ac.kr Lee4Hyo Youl  MoonHyo Youl Moon1*
  • 1Seoul National University, Seoul, Republic of Korea
  • 2Hallym University, Chuncheon-si, Gangwon, Republic of Korea
  • 3Sungkyunkwan University, Jongno-gu, Seoul, Republic of Korea
  • 4CHA University, Seongnam, Gyeonggi, Republic of Korea

The final, formatted version of the article will be published soon.

Background: In ischemic stroke (IS) pathology, neutrophils are recruited and worsen the disease conditions by releasing the amount of neutrophil extracellular traps (NETs). Previous studies have demonstrated that alleviating IS is associated with reduced accumulated neutrophils and NET levels. Notably, exercise preconditioning (EP) has the potential to modulate neutrophil function, thereby contributing to the ameliorate of IS. This study compared the functional differences between resting and exercise-preconditioned neutrophils under IS pathology.Methods: 8-week-old C57BL/6J male mice underwent 8 weeks of voluntary exercise before photothrombotic ischemic stroke (PTI) surgery. Behavioral tests were conducted to verify the effects of EP on acute recovery following PTI. A migration assay was performed to assess the migration capacity of blood-isolated neutrophils under IS. Plasma NET levels were quantified using enzymelinked immunosorbent assay (ELISA), while NET presence in the brain was evaluated through immunofluorescence (IF) staining.Results: Exercise-preconditioned-PTI (Ex-PTI) mice showed superior behavioral outcomes in grip strength and open field tests both before and 2 days after PTI compared to sedentary-PTI (Sed-PTI) mice. Furthermore, EP reduced the migration capacity of neutrophils and decreased the NETs formations in both plasma and brain 2 days after PTI surgery.Our study demonstrates that EP enhances acute recovery in IS and may beneficially orchestrate IS pathology by inhibiting migratory capacity and reducing NET formation in vivo.

Keywords: Exercise preconditioning1, Neutrophil extracellular traps2, Migration capacity3, Photothrombotic ischemic stroke4, Voluntary exercise5

Received: 20 Feb 2025; Accepted: 19 May 2025.

Copyright: © 2025 Kim, Cho, Park, Woo, Yuk, Yi, Jeong, Jeon, Bae, Lee and Moon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hyo Youl Moon, Seoul National University, Seoul, Republic of Korea

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