del Río, CarmenMontaner, Joan2022-09-262022-09-262021-10-15Del Río C, Montaner J. Hypoxia Tolerant Species: The Wisdom of Nature Translated into Targets for Stroke Therapy. Int J Mol Sci. 2021 Oct 15;22(20):111311661-6596http://hdl.handle.net/10668/4141Human 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/StrokeNeuroprotectionHypoxia toleranceStroke therapyCell deathIschemiaAccidente cerebrovascularNeuroprotecciónHipoxiaMuerte celularIsquemiaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain InjuriesMedical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Helminths::Nematoda::Secernentea::Rhabditida::Rhabditoidea::Caenorhabditis::Caenorhabditis elegansMedical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Arthropods::Insects::Diptera::Drosophilidae::DrosophilaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Molecular Targeted TherapyMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective AgentsMedical Subject Headings::Phenomena and Processes::Biological Phenomena::Species SpecificityMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::StrokeMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::NeuronsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DeathMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Brain IschemiaMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Brain Ischemia::Hypoxia-Ischemia, BrainMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, TheoreticalMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Vascular Surgical Procedures::Thrombectomyreview article34681788open access10.3390/ijms2220111311422-0067PMC8537001