Related Experiment Video
Updated: May 16, 2026
07:34
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
[CREB activation is a key player for ischemic tolerance in the brain].
Kazuo Kitagawa1, Tsutomu Sasaki, Yasukazu Terasaki
1Department of Neurology, Osaka University Graduate School of Medicine.
Rinsho Shinkeigaku = Clinical Neurology
|December 1, 2012
Summary
Ischemic tolerance protects the brain like hypothermia. This involves CREB activation, a transcription factor crucial for neuronal survival, by regulating gene expression of survival factors.
Area of Science:
- Neuroscience
- Molecular Biology
Context:
- Ischemic tolerance offers neuroprotection comparable to hypothermia.
- Several pathways contribute to ischemic tolerance.
- CREB (cAMP response element-binding protein) is a key transcription factor for neuronal survival and plasticity.
Purpose:
- To elucidate the molecular mechanisms underlying ischemic tolerance.
- To investigate the role of CREB activation in neuroprotection during ischemia.
Summary:
- Ischemia triggers glutamate release, activating NMDA receptors and calcium influx.
- Calcium-calmodulin dependent protein kinase (CaMK) phosphorylates CREB and salt-inducible kinase (SIK).
- SIK degradation leads to CRTC1 nuclear translocation, enhancing CREB-mediated transcription of survival genes and conferring resistance to subsequent ischemia.
Impact:
- Identifies a novel molecular pathway involving SIK and CRTC1 in CREB-mediated ischemic tolerance.
- Provides a deeper understanding of neuroprotective mechanisms against ischemic injury.
- Offers potential therapeutic targets for stroke and other ischemic conditions.
Related Concept Videos
01:15Ischemic 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...
01:15Ischemic 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.
01:17Ischemic 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...
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...