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J Exp Biol. 2014 Apr 1;217(Pt 7):1024-39. doi: 10.1242/jeb.085381.

No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates.

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Psychiatric Institute, Department of Psychiatry and Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois, Chicago, IL 60612, USA.


Many vertebrates are challenged by either chronic or acute episodes of low oxygen availability in their natural environments. Brain function is especially vulnerable to the effects of hypoxia and can be irreversibly impaired by even brief periods of low oxygen supply. This review describes recent research on physiological mechanisms that have evolved in certain vertebrate species to cope with brain hypoxia. Four model systems are considered: freshwater turtles that can survive for months trapped in frozen-over lakes, arctic ground squirrels that respire at extremely low rates during winter hibernation, seals and whales that undertake breath-hold dives lasting minutes to hours, and naked mole-rats that live in crowded burrows completely underground for their entire lives. These species exhibit remarkable specializations of brain physiology that adapt them for acute or chronic episodes of hypoxia. These specializations may be reactive in nature, involving modifications to the catastrophic sequelae of oxygen deprivation that occur in non-tolerant species, or preparatory in nature, preventing the activation of those sequelae altogether. Better understanding of the mechanisms used by these hypoxia-tolerant vertebrates will increase appreciation of how nervous systems are adapted for life in specific ecological niches as well as inform advances in therapy for neurological conditions such as stroke and epilepsy.


Arctic ground squirrel; Cetacean; Hypoxia; Naked mole-rat; Seal; Turtle

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