Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest

Abstract

Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague–Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA.

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

“…Usually, ACA was confirmed at 3-4 min after vecuronium bromide injection in this study. Perfect ACA was confirmed when pulseless electric activity (PEA) was shown and mean arterial pressure (MAP) was below 25 mmHg [8,9]. ACA was maintained for 5 min.…”

“…Subsequently, manual chest compressions were performed. Namely, manual chest compression was performed at a rate of 300/min until MAP increased to 60 mmHg, and electrocardiography was checked [8,9]. Once each rat breathed and was hemodynamically stable, which was usually shown 1 h after ROSC, the catheter was removed.…”

“…Body weight and MAP between the groups were compared at 1 day after ROSC. Motor function of the hind limbs was evaluated for paralysis at 1 day after ROSC using Tarlov Scale [8]: motor deficit scoring 0, complete paralysis with no hind limb function; 1, slight movement in articulations; 2, unable to stand without support; 3, sit alone; 4, weak walking with poor jumping; 5, normal walking.…”

“…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.…”

Effects of hypothermia on inflammatory cytokine expression in rat liver following asphyxial cardiac arrest

“…To date, it has been reported that hypothermic therapy can effectively reduce the histopathological damage of lumbar spinal cord (18,19), hippocampus (20) and cerebellum (21) in the brain of a rat model of asphyxial CA. However, as aforementioned, few studies have examined the effects of hypothermia on the liver after CA.…”