Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (12): 2007-2013.doi: 10.4103/1673-5374.221157

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Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat hippocampus in the early period of asphyxia-induced cardiac arrest under normothermia

Hyun-Jin Tae1, Il Jun Kang2, Tae-Kyeong Lee3, Jeong Hwi Cho3, Jae-Chul Lee3, Myoung Cheol Shin4, Yoon Sung Kim4, 5, Jun Hwi Cho4,Jong-Dai Kim6, Ji Hyeon Ahn7, Joon Ha Park7, In-Shik Kim1, Hyang-Ah Lee8, Yang Hee Kim9, Moo-Ho Won3, Young Joo Lee10   

  1. 1 Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, South Korea
    2 Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea
    3 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
    4 Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea
    5 Department of Emergency Medicine, Samcheok Medical Center, Samcheok, South Korea
    6 Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, South Korea
    7 Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea
    8 Department of Obstetrics and Gynecology, School of Medicine, Kangwon National University, Chuncheon, South Korea
    9 Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, South Korea
    10 Department of Emergency Medicine, Seoul Hospital, College of Medicine, Sooncheonhyang University, Seoul, South Korea
  • Received:2017-11-13 Online:2017-12-15 Published:2017-12-15
  • Contact: Moo-Ho Won, D.V.M., Ph.D.or Young Joo Lee, M.D., Ph.D.,mhwon@kangwon.ac.kr or brugada@naver.com.
  • Supported by:

    This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF),the Ministry of Education (NRF-2014R1A1A2057263), by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017R1A2B4009079 & NRF-2017R1A2B4008403), and by the Bio-Synergy Research Project (NRF-2015M3A9C4076322) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.

Abstract:

Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest (CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet (CV) and Fluore-Jade B (F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-alpha (TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA (about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day post-CA, and they were activated (enlarged cell bodies with short and thicken processes) in all layers 2 days post-CA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-αimmunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.

Key words: nerve regeneration, post-cardiac arrest syndrome, normothermia, neuronal damage, gliosis, tumor necrosis factor-alpha, neural regeneration