Long-Term Alternating Fasting Increases Interleukin-13 in the Gerbil Hippocampus, But Does Not Protect BBB and Pyramidal
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ORIGINAL PAPER
Long‑Term Alternating Fasting Increases Interleukin‑13 in the Gerbil Hippocampus, But Does Not Protect BBB and Pyramidal Neurons From Ischemia–Reperfusion Injury Tae‑Kyeong Lee1 · Yoonsoo Park2 · Bora Kim3 · Jae‑Chul Lee3 · Myoung Cheol Shin2 · Taek Geun Ohk2 · Chan Woo Park2 · Jun Hwi Cho2 · Joon Ha Park4 · Choong Hyun Lee5 · Moo‑Ho Won3 · Ji Hyeon Ahn1,3 Received: 19 March 2020 / Revised: 7 July 2020 / Accepted: 8 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract It is questionable whether intermittent fasting (IF) protects against brain ischemic injury. This study examined whether IF increased anti-inflammatory cytokines and protected neurons from ischemia–reperfusion injury in the gerbil hippocampus. Gerbils were subjected to 1-day alternating fasting as IF for 1, 2, or 3 months and assigned to sham or 5 min of transient ischemia. We examined the changes in anti-inflammatory cytokines (IL-4 and IL-13), neurons and IgG by immunohistochemistry or immunofluorescence staining in the cornu ammonis 1 (CA1) region of the hippocampus before and after ischemia. IF increased IL-13 immunoreactivity in the CA1 region before ischemia, but did not affect IL-4 immunoreactivity. After ischemia, IL-13 and 4 immunoreactivities in the CA1 region were significantly lower in IF gerbils than in non-IF gerbils. In the IF gerbils, the CA1 pyramidal neurons were not protected from ischemic injury; in these gerbils, strong IgG immunoreactivity was seen in the CA1 parenchyma, indicating leakage of the BBB. In brief, IF increased IL-13 in the CA1 region, but these neurons were not protected from transient ischemic injury evidenced by IgG immunoreactivity in the CA1 parenchyma. This study indicates that IF increased some anti-inflammatory cytokines but did not afford neuroprotection against ischemic insults via BBB disruption. Keywords Anti-inflammatory cytokine · BBB leakage · IL-13 · Intermittent fasting · Neuroprotection · Transient global cerebral ischemia
Introduction
Tae-Kyeong Lee and Yoonsoo Park contributed equally to this article. * Moo‑Ho Won [email protected] * Ji Hyeon Ahn jh‑[email protected] 1
2
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea Department of Emergency Medicine, and Institute of Medical Sciences, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
The dysregulation of inflammatory cytokines contributes to neuroinflammatory processes, which cause neuronal damage after an injury to the nervous system. Anti-inflammatory cytokines, such as interleukin (IL)-4 and IL-13 are involved in the resolution of neuroinflammation. Specifically, they 3
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
4
Department of Anatomy, College of Oriental Medicine, Dongguk University-Gyeongju, Gyeongju, Gyeon
