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.
Footnotes
Funding
J.L. was supported by grants from the National Science Foundation [grant number 744979]; and the US Army Medical Research and Materiel Command [grant number 10917352). S.L.M. was supported by the National Institutes of Health [grant number 1R15AG033374-01]; the American Heart Association; the American Federation of Aging Research; and the Florida Atlantic University Foundation. K.L.D. was supported by the US Army Research Office [grant number W911NF-05-1-0280]; The US Army Medical Research and Materiel Command [grant number 05178001]; the National Institute of Neurological Disorders and Stroke [grant numbers NS041069-06 and R15NS070779]; and Alaska IDeA Networks of Biomedical Research Excellence and Alaska Experimental Program to Stimulate Competitive Research. L.P.F. was supported by the Norwegian Research Council [grant number 164791/V40]; and the work on neuroglobin by grants from Deutsche Forschungsgemeinschaft to Dr Thorsten Burmester [grant numbers Bu956/10, Bu956/12; Ha2103/3]. T.J.P. was supported by the National Science Foundation [grant number 744979]; and a generous gift from a foundation that prefers to remain anonymous. Deposited in PMC for release after 12 months.
