Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan 50510, Korea.
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
Cells. 2021 Jan 2;10(1):60. doi: 10.3390/cells10010060.
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.
中枢神经系统（CNS）自主功能障碍可导致心脏骤停（CA）后复苏患者死亡。然而，关于 CA 动物模型的组织病理学变化的研究甚少。在本研究中，我们研究了窒息性 CA 后早期各种脑区和脊髓神经元死亡和损伤的发生率，并研究了 CA 后低温治疗与神经元损伤之间的死亡率的关系。大鼠经历 7-8 分钟的窒息性 CA，随后进行复苏和即刻低温治疗。使用亚甲蓝（Nissl 物质标志物）和氟嗪 B（神经元死亡标志物）检查与自主控制相关的 8 个区域（扣带回皮质、海马体、丘脑、下丘脑、延髓和脊髓）。CA 后 1 天的存活率为 44.5%，2 天为 18.2%，5 天为 0%。CA 后 12 小时，在延髓的巨细胞网状核和尾侧腹外侧网状核以及颈、胸、腰和骶脊髓的 VII 层中开始出现神经元死亡，这些神经元与自主下运动神经元有关。在这些区域，CA 后随时间推移，Iba-1 免疫反应性（小胶质细胞活化）逐渐增加。及时低温治疗可提高 CA 后 5 天的存活率，减轻损伤区域神经元的损伤和死亡。然而，CA 后 12 天的存活率仍为 0%。综上所述，本研究表明，与自主下运动神经元有关的神经元的早期损伤和死亡与 CA 后高死亡率显著相关，及时低温治疗可暂时提高 CA 后的存活率，但不能最终挽救动物。
