Hypoxia, hibernation and Neuroprotection: An Experimental Study in Mice

摘要

Hibernation is a unique physiological state that evolved to survive periods of food shortages. It is characterized by profound decreases in metabolic rate, body temperature and physiological functions. Studies have shown that animals in hibernation can resist neurological damage. Here, we aimed to study whether hypoxia can induce a hibernation-like state in a traditionally non-hibernating animal and whether it is neuroprotective. All procedures were conducted according to international guidelines on laboratory animal safety. Mice C57BL/6 (19-21g) were placed into a 125 mL jar with fresh air and the jar was sealed with a rubber plug. For each run, the tolerance limit was judged by the animals’ appearance for "air hunger”. The animal was removed from the jar as soon as its first gasping breath appeared and was moved to another fresh-air-containing jar of similar volume. This procedure was performed in four runs. The hypoxia exposure significantly decreased oxygen (O2) consumption, carbon dioxide (CO2) production, respiratory rate and heart rate. Meanwhile, rectal temperature reached a minimum of 12.7±2.56°C, which is lower than a wide range of ambient temperatures. The mimicked hibernation decreased the infarct size in a focal cerebral ischemia mouse model. Our findings suggest the possibility of inducing suspended animation-like hibernation states for medical applications post injury.