Related Experiment Video
Updated: May 15, 2026
06:36
Using Zebrafish Larvae to Study the Pathological Consequences of Hemorrhagic Stroke
Published on: June 5, 2019
Kruppel-like factor 2 protects against ischemic stroke by regulating endothelial blood brain barrier function
Hong Shi1, Baiyang Sheng, Feng Zhang
1Harrington Heart and Vascular Institute, Case Cardiovascular Research Institute, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|January 22, 2013
Summary
Kruppel-like factor 2 (KLF2) protects the blood-brain barrier (BBB) during ischemic stroke. Loss of KLF2 worsens stroke damage, while its overexpression offers protection, highlighting KLF2 as a novel therapeutic target.
Area of Science:
- Neuroscience
- Vascular Biology
- Molecular Biology
Background:
- Ischemic stroke disrupts brain endothelial function, leading to blood-brain barrier (BBB) breakdown and neuronal death.
- Kruppel-like factor 2 (KLF2) is a flow-regulated transcription factor crucial for endothelial health.
Purpose of the Study:
- To investigate the role of KLF2 in cerebrovascular function and ischemic stroke pathogenesis.
- To determine if KLF2 influences BBB integrity and neuroprotection.
Main Methods:
- Transient middle cerebral artery occlusion in KLF2-deficient, KLF2 overexpressing, and control mice.
- Assessment of stroke volume, BBB function via PET imaging and Evan's blue assay.
- In vitro studies using primary brain microvascular endothelial cells (ECs).
Main Results:
- KLF2-deficient mice showed larger stroke volumes and impaired BBB function.
- KLF2 overexpressing mice were protected against stroke with preserved BBB function.
- KLF2 regulates occludin, a key BBB tight junction factor, in both in vitro and in vivo models.
Conclusions:
- Endothelial KLF2 is a critical regulator of the BBB.
- KLF2 exhibits significant neuroprotective effects in the context of ischemic stroke.
- Targeting KLF2 represents a potential therapeutic strategy for stroke treatment.
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...
00:49The Blood-brain Barrier
Overview
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
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.
01:29Hemorrhagic Stroke ll: Pathophysiology
A hemorrhagic stroke develops when a cerebral blood vessel ruptures, allowing blood to escape into the surrounding brain tissue, as in intracerebral hemorrhage (ICH), or into the subarachnoid space, as in subarachnoid hemorrhage (SAH). Because the skull is a rigid compartment, the sudden presence of extravascular blood rapidly increases intracranial pressure and compresses adjacent neural structures, leading to immediate tissue injury and impaired cerebral perfusion.Mass Effect and Primary...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...