Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (8): 1394-1403.doi: 10.4103/1673-5374.253524

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Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia

Tae-Kyeong Lee 1 , Hyunjung Kim 1 , Minah Song 1 , Jae-Chul Lee 1 , Joon Ha Park 2 , Ji Hyeon Ahn 2 , Go Eun Yang 3 , Hyeyoung Kim 4, 5 , Taek Geun Ohk 5 , Myoung Cheol Shin 5 , Jun Hwi Cho 5 , Moo-Ho Won 1   

  1. 1 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
    2 Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon, Republic of Korea
    3 Department of Radiology, Kangwon National University Hospital, Chuncheon, Gangwon, Republic of Korea
    4 Department of Anesthesiology and Pain Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju Chungcheongbuk, Republic of Korea
    5 Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
  • Online:2019-08-15 Published:2019-08-15
  • Contact: Moo-Ho Won, DVM, PhD, mhwon@kangwon.ac.kr; Jun Hwi Cho, MD, PhD, cjhemd@kangwon.ac.kr.
  • Supported by:

    This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B01011790; to JHC); Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017R1A2B4009079; to MHW), and by Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01329401; to MHW) Rural Development Administration, Republic of Korea.

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Abstract:

Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1–3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Iba1) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1–3 region 2 days later and granule cell death in hippocampal dentate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5-minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No., KW-180124-1) on May 22, 2018.

Key words: transient global brain ischemia, delayed neuronal death, glial activation, ischemic duration, hippocampus, spontaneous motor activity, Mongolian gerbil, histology, neural regeneration