Abstract
Human neurons rapidly die after ischemia and current therapies for stroke management are limited to restoration of blood flow to prevent further brain damage. Thrombolytics and mechanical thrombectomy are the available reperfusion treatments, but most of the patients remain untreated. Neuroprotective therapies focused on treating the pathogenic cascade of the disease have widely failed. However, many animal species demonstrate that neurons can survive the lack of oxygen for extended periods of time. Here, we reviewed the physiological and molecular pathways inherent to tolerant species that have been described to contribute to hypoxia tolerance. Among them, Foxo3 and Eif5A were reported to mediate anoxic survival in Drosophila and Caenorhabditis elegans, respectively, and those results were confirmed in experimental models of stroke. In humans however, the multiple mechanisms involved in brain cell death after a stroke causes translation difficulties to arise making necessary a timely and coordinated control of the pathological changes. We propose here that, if we were able to plagiarize such natural hypoxia tolerance through drugs combined in a pharmacological cocktail it would open new therapeutic opportunities for stroke and likely, for other hypoxic conditions.
Highlights
This phenomenon disrupts the integrity of the vascular blood brain barrier (BBB) and helps immune cells to migrate and infiltrate the brain parenchyma, which contributes to the inflammatory response initiated a few hours after anoxia [1]
Neurons from other animal species can survive the lack of oxygen but the complexity that human brain has achieved during evolution make us more vulnerable to the energetic failure during ischemia
This review summarizes the current knowledge on the mechanisms that allow for brain hypoxia tolerance of the main resistant species, including several mammals such as diving mammals and the naked mole rat
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. There are fascinating examples in nature of animals exceptionally tolerant to the lack of oxygen which cope with extreme environmental conditions that would be lethal to humans, such as pond turtles and crucian carps, that can survive anoxia under ice-covered lakes and ponds for several months. In such conditions temperatures are close to 0 ◦ C and clearly contribute to the extreme tolerance in both species, but even at higher temperatures they can still survive anoxia for at least a day or two [4]. Understanding the mechanisms that operate simultaneously in tolerant animals to grant them survive hypoxia without neurological damage may yield different insights to propose new neuroprotective combination therapies for stroke that overcome the failure of individual treatments (Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
