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

Abstract

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.

Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation

“…In a rat model of ACA/CPR, neuronal death (loss) in the anterior horn in the lumbar part of the spinal cord occurs at one day after ACA/CPR [9]. In addition, Ahn et al [10] recently reported that neuronal death in the central nervous system (CNS) autonomic control center (myelencephalon and thoracolumbar division of the spinal cord) occurred very early compared to the other CNS divisions after ACA/CPR in rats. In our current study, we found that ventral motor neurons at the level of the lumbar spinal cord were dead at two days after ACA/CPR in rats.…”

“…It has been reported that CA is one of the causes of severe spinal cord injuries including paraplegia, which negatively affects the quality of life in patients [5][6][7]. It is well known that motor neurons located in the ventral horn of the spinal cord are very vulnerable to ischemia-reperfusion injury [8][9][10]. However, the factors protecting or attenuating the damage of spinal motor neurons following ischemic insults have been insufficiently reported yet.…”

Hypothermic treatment reduces matrix metalloproteinase-9 expression and damage in the liver following asphyxial cardiac arrest in rats

“…ACA induced according to the published protocols [ 45 , 46 ]. In brief, rats were anesthetized with 2.5% isoflurane in oxygen (33%) and nitrous oxide (67%), and the rats were endotracheally intubated with cannula (14-gauge) and maintained to ventilate respiration using a rodent ventilator (Harvard Apparatus, Holliston, MA, USA).…”

“…CPR was performed according to the published protocols [ 45 , 46 ]. In brief, CPR was performed from 5 min after ACA as follows.…”

“…Hypothermic therapy was conducted according to the published protocol [ 45 , 46 ]. In short, hypothermia was conducted promptly after ROSC by surface cooling with isopropyl alcohol wipes.…”