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.
Highlights
Vascular spinal disorders, non-traumatic spinal cord injuries, originate from tumors or cardiovascular disorders, and the spinal cord is vulnerable to ischemic damage [1]
In the present study, we investigated possible mechanisms of therapeutic hypothermia in the asphyxial CA (ACA)-induced lumbar spinal cord ischemia by referring to previous studies
It has been reported that ischemic vulnerability of the lumbar spinal region is considerably high compared to the other regions [4] since much energy may be required for extensive activity of motor neurons in the lumbosacral spinal region [26]
Summary
Non-traumatic spinal cord injuries, originate from tumors or cardiovascular disorders, and the spinal cord is vulnerable to ischemic damage [1]. Global ischemia after cardiac arrest (CA) causes a temporary interruption of the blood supply to the spinal arteries and results in neuronal damage in the spinal cord, which can lead to severe clinical symptoms, such as paralysis and sensory dysfunction [2]. Studies on damage in the spinal cord after asphyxial CA (ACA), which is apparently different from spinal cord ischemia, are still lacking compared to studies on spinal cord injury after spinal cord ischemia. Inconsistent results in the distribution pattern of neuronal damage in the lumbar spinal cord after CA have been reported. Studies on damage in the spinal cord after ACA are still lacking compared to studies on spinal cord injury after spinal cord ischemia
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