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Harnessing hypoxic adaptation to prevent, treat, and repair stroke

The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being hi...

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Autores principales: Ratan, Rajiv R., Siddiq, Ambreena, Smirnova, Natalya, Karpisheva, Ksenia, Haskew-Layton, Renee, McConoughey, Stephen, Langley, Brett, Estevez, Alvaro, Huerta, Patricio T., Volpe, Bruce, Roy, Sashwati, Sen, Chandan K., Gazaryan, Irina, Cho, Sunghee, Fink, Matthew, LaManna, Joseph
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121656/
https://www.ncbi.nlm.nih.gov/pubmed/18043901
http://dx.doi.org/10.1007/s00109-007-0283-1
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author Ratan, Rajiv R.
Siddiq, Ambreena
Smirnova, Natalya
Karpisheva, Ksenia
Haskew-Layton, Renee
McConoughey, Stephen
Langley, Brett
Estevez, Alvaro
Huerta, Patricio T.
Volpe, Bruce
Roy, Sashwati
Sen, Chandan K.
Gazaryan, Irina
Cho, Sunghee
Fink, Matthew
LaManna, Joseph
author_facet Ratan, Rajiv R.
Siddiq, Ambreena
Smirnova, Natalya
Karpisheva, Ksenia
Haskew-Layton, Renee
McConoughey, Stephen
Langley, Brett
Estevez, Alvaro
Huerta, Patricio T.
Volpe, Bruce
Roy, Sashwati
Sen, Chandan K.
Gazaryan, Irina
Cho, Sunghee
Fink, Matthew
LaManna, Joseph
author_sort Ratan, Rajiv R.
collection PubMed
description The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics.
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spelling pubmed-21216562007-12-17 Harnessing hypoxic adaptation to prevent, treat, and repair stroke Ratan, Rajiv R. Siddiq, Ambreena Smirnova, Natalya Karpisheva, Ksenia Haskew-Layton, Renee McConoughey, Stephen Langley, Brett Estevez, Alvaro Huerta, Patricio T. Volpe, Bruce Roy, Sashwati Sen, Chandan K. Gazaryan, Irina Cho, Sunghee Fink, Matthew LaManna, Joseph J Mol Med Review The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics. Springer-Verlag 2007-11-28 2007-12 /pmc/articles/PMC2121656/ /pubmed/18043901 http://dx.doi.org/10.1007/s00109-007-0283-1 Text en © The Author(s) 2007
spellingShingle Review
Ratan, Rajiv R.
Siddiq, Ambreena
Smirnova, Natalya
Karpisheva, Ksenia
Haskew-Layton, Renee
McConoughey, Stephen
Langley, Brett
Estevez, Alvaro
Huerta, Patricio T.
Volpe, Bruce
Roy, Sashwati
Sen, Chandan K.
Gazaryan, Irina
Cho, Sunghee
Fink, Matthew
LaManna, Joseph
Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title_full Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title_fullStr Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title_full_unstemmed Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title_short Harnessing hypoxic adaptation to prevent, treat, and repair stroke
title_sort harnessing hypoxic adaptation to prevent, treat, and repair stroke
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121656/
https://www.ncbi.nlm.nih.gov/pubmed/18043901
http://dx.doi.org/10.1007/s00109-007-0283-1
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