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Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
Ischemic Heart Disease: Overview01:17

Ischemic Heart Disease: Overview

Ischemic heart disease occurs when the heart's blood supply dwindles, causing an ominous lack of oxygen and nutrients. This deficiency, stemming from reduced or obstructed blood flow, spells danger, leading to heart muscle damage and dysfunction.
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and narrowing...
Ischemic Stroke l: Introduction01:15

Ischemic Stroke l: Introduction

Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.

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Articles linked to this work by shared authors, journal, and citation graph.

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Integrative transcriptomic and metabolic analyses of the mammalian hibernating brain identifies a key role for succinate dehydrogenase in ischemic tolerance.

bioRxiv : the preprint server for biology·2023
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The Role of SUMOylation and Ubiquitination in Brain Ischaemia: Critical Concepts and Clinical Implications.

Current issues in molecular biology·2019
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Molecular signature of penumbra in acute ischemic stroke: a pilot transcriptomics study.

Annals of clinical and translational neurology·2019
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SUMOylation promotes survival and integration of neural stem cell grafts in ischemic stroke.

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Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology·2018
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Drugging SUMOylation for neuroprotection and oncotherapy.

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Related Experiment Video

Updated: May 10, 2026

Bilateral Common Carotid Artery Occlusion as an Adequate Preconditioning Stimulus to Induce Early Ischemic Tolerance to Focal Cerebral Ischemia
07:46

Bilateral Common Carotid Artery Occlusion as an Adequate Preconditioning Stimulus to Induce Early Ischemic Tolerance to Focal Cerebral Ischemia

Published on: May 9, 2013

SUMO and ischemic tolerance.

Yang-ja Lee1, John M Hallenbeck

  • 1Stroke Branch, National Institute of Neurological Disease and Stroke, National Institutes of Health (NINDS/NIH), Bldg10/Rm5B06, MSC 1401, 10 Center Drive, Bethesda, MD, 20892, USA, wicknery@ninds.nih.gov.

Neuromolecular Medicine
|June 19, 2013
PubMed
Summary

Hibernating squirrels exhibit natural tolerance to ischemia by increasing small ubiquitin-like modifier (SUMO) and other ubiquitin-like modifier (ULM) conjugations in the brain. These modifications protect tissues during low blood flow, offering insights into stroke therapies.

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Last Updated: May 10, 2026

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Hibernating squirrels display remarkable tolerance to ischemia, a condition of reduced blood flow.
  • This natural tolerance is linked to significant changes in protein modification within the brain during torpor.
  • Small ubiquitin-like modifiers (SUMO) and other ubiquitin-like modifiers (ULMs) are key players in cellular stress responses.

Purpose of the Study:

  • To investigate the role of SUMOylation and other ULM conjugations in the ischemic tolerance observed in hibernating squirrels.
  • To explore the mechanisms by which these modifications confer cytoprotection.
  • To identify potential therapeutic targets for stroke based on these findings.

Main Methods:

  • Analysis of SUMOylation and ULM conjugation levels in the brains of hibernating squirrels during torpor.
  • Investigating the effects of SUMO and Ubc9 (SUMO E2 conjugating enzyme) manipulation on cellular responses to ischemic stress in cell culture models.
  • Examining the role of specific microRNAs (miRNAs) in regulating ULM conjugation levels.

Main Results:

  • Massive SUMOylation (SUMO-1 and SUMO-2/3) and increased global ULM conjugations were observed in hibernating squirrel brains during torpor.
  • Ischemic stress increased SUMO conjugation, particularly SUMO-2/3, during reperfusion and reoxygenation.
  • Elevated SUMOylation conferred cytoprotection against ischemic insults, while reduced SUMOylation increased sensitivity.
  • Specific miRNAs, including the miR-200 and miR-182 families, were found to control ULM conjugation levels.

Conclusions:

  • Hibernating squirrels achieve natural ischemic tolerance through enhanced SUMOylation and ULM conjugations in the brain.
  • These modifications play a crucial cytoprotective role against ischemia.
  • Targeting specific miRNAs that regulate these conjugations may offer a novel therapeutic strategy for stroke and other ischemic conditions.