Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.
The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply.
University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States. Electronic address: tinathaniel@gmail.com.
Thomas I
TI
Nathaniel
University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States.
Ashley
A
Williams-Hernandez
University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States.
Anan L
AL
Hunter
University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States.
Caroline
C
Liddy
University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States.
Dennis M
DM
Peffley
Chemistry department, John Brown University, 2000 W. University Street, Siloam Springs, AR 72761, United States.
Francis E
FE
Umesiri
Department of Biology, North Greenville University, 7801 North Tigerville Road, Tigerville, SC 29688, United States.
Adebobola
A
Imeh-Nathaniel
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism*
Hypoxia; Metabolic suppression; Neuroprotection; Stroke