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Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models
Thomas I Nathaniel1, Ashley Williams-Hernandez1, Anan L Hunter1
1University of South Carolina School of Medicine-Greenville, 701 Grove Road, Greenville, SC 29605, United States.
Abstract:
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.
Insights
Exploring unconventional animal models reveals novel strategies for treating hypoxic/ischemic brain injury in stroke patients. These models offer insights into regulating brain metabolism and oxygenation during stroke, crucial for developing new neuroprotective therapies.
Area of Science:
- Neuroscience
- Comparative Physiology
- Stroke Research
Background:
- Hypoxic/ischemic brain injury in stroke is a major global health challenge.
- Despite extensive research, effective neuroprotective treatments for acute ischemic stroke remain elusive.
- Current treatments like thrombolysis have limited time windows and patient applicability.
Purpose of the Study:
- To review novel insights into resisting tissue hypoxia from unconventional animal models.
- To explore how these animal models can inform strategies for clinical management of stroke-related hypoxia.
- To identify physiological and molecular adaptations for hypoxia tolerance.
Main Methods:
- Review of literature on hypoxia-tolerant animal models.
- Analysis of adaptations in species like the naked mole-rat and arctic ground squirrel.
- Examination of physiological and molecular mechanisms of hypoxia resistance.
Main Results:
- Unconventional animal models demonstrate unique abilities to regulate brain metabolism and oxygenation under hypoxic conditions.
- Species like the naked mole-rat actively manage metabolic activity to defend against oxidative stress.
- The arctic ground squirrel's brain remains oxygenated during hypoxia without cellular stress.
Conclusions:
- Insights from animal models offer potential new therapeutic strategies for stroke patients.
- Understanding hypoxia tolerance mechanisms can guide the development of treatments for conditions where oxygen supply is insufficient.
- Further research into these adaptations may unlock novel approaches to neuroprotection in stroke.
