Neuronal Death in the CNS Autonomic Control Center Comes Very Early after Cardiac Arrest and Is Not Significantly Attenuated by Prompt Hypothermic Treatment in Rats
Ji Hyeon Ahn,
Tae-Kyeong Lee,
Hyun-Jin Tae,
Bora Kim,
Hyejin Sim,
Jae-Chul Lee,
Dae Won Kim,
Yoon Sung Kim,
Myoung Cheol Shin,
Yoonsoo Park,
Jun Hwi Cho,
Joon Ha Park,
Choong-Hyun Lee,
Soo Young Choi,
Moo-Ho Won
Affiliations
Ji Hyeon Ahn
Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan 50510, Korea
Tae-Kyeong Lee
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea
Hyun-Jin Tae
Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Korea
Bora Kim
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Hyejin Sim
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Jae-Chul Lee
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Dae Won Kim
Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung 25457, Korea
Yoon Sung Kim
Department of Emergency Medicine, Samcheok Medical Center, Samcheok 25920, Korea
Myoung Cheol Shin
Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Yoonsoo Park
Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Jun Hwi Cho
Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Joon Ha Park
Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea
Choong-Hyun Lee
Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Korea
Soo Young Choi
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea
Moo-Ho Won
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
Autonomic dysfunction in the central nervous system (CNS) can cause death after recovery from a cardiac arrest (CA). However, few studies on histopathological changes in animal models of CA have been reported. In this study, we investigated the prevalence of neuronal death and damage in various brain regions and the spinal cord at early times after asphyxial CA and we studied the relationship between the mortality rate and neuronal damage following hypothermic treatment after CA. Rats were subjected to 7–8 min of asphyxial CA, followed by resuscitation and prompt hypothermic treatment. Eight regions related to autonomic control (the cingulate cortex, hippocampus, thalamus, hypothalamus, myelencephalon, and spinal cord) were examined using cresyl violet (a marker for Nissl substance) and Fluoro-Jade B (a marker for neuronal death). The survival rate was 44.5% 1 day post-CA, 18.2% 2 days post-CA and 0% 5 days post-CA. Neuronal death started 12 h post-CA in the gigantocellular reticular nucleus and caudoventrolateral reticular nucleus in the myelencephalon and lamina VII in the cervical, thoracic, lumbar, and sacral spinal cord, of which neurons are related to autonomic lower motor neurons. In these regions, Iba-1 immunoreactivity indicating microglial activation (microgliosis) was gradually increased with time after CA. Prompt hypothermic treatment increased the survival rate at 5 days after CA with an attenuation of neuronal damages and death in the damaged regions. However, the survival rate was 0% at 12 days after CA. Taken together, our study suggests that the early damage and death of neurons related to autonomic lower motor neurons was significantly related to the high mortality rate after CA and that prompt hypothermic therapy could increase the survival rate temporarily after CA, but could not ultimately save the animal.
