Related Experiment Video

Updated: Jul 13, 2026

A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction
04:29

A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction

Published on: May 17, 2024

Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia

Gary A Rosenberg1, Yi Yang

  • 1Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-0001, USA. Grosenberg@salud.unm.edu

Neurosurgical Focus
|July 7, 2007
PubMed

Insights

Cerebral ischemia damages the blood-brain barrier (BBB) via matrix metalloproteinases (MMPs). While MMP inhibitors initially protect the BBB, they hinder recovery, necessitating new therapeutic strategies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Cerebral ischemia induces cell swelling and blood-brain barrier (BBB) disruption.
  • Vasogenic edema arises from blood vessel damage, distinct from cytotoxic edema due to energy failure.
  • Matrix metalloproteinases (MMPs) are key enzymes that degrade extracellular matrix and compromise BBB integrity.

Purpose of the Study:

  • To investigate the role of MMPs in BBB breakdown during cerebral ischemia and reperfusion.
  • To evaluate the efficacy of MMP inhibitors in protecting the BBB.
  • To identify therapeutic targets for preventing vasogenic edema without impeding neurological recovery.

Main Methods:

  • Analysis of MMP activation and activity following cerebral ischemia.
  • Assessment of BBB integrity, including tight junction proteins and basal lamina components.
  • Evaluation of the effects of synthetic MMP inhibitors on BBB opening and recovery processes.

Main Results:

  • MMPs, particularly MMP-2, MMP-9, and MMP-3, are implicated in the biphasic opening of the BBB after reperfusion.
  • Synthetic MMP inhibitors can restore early BBB integrity but are ineffective against later, more severe damage.
  • These inhibitors also impede angiogenesis and neurogenesis, thereby slowing functional recovery.

Conclusions:

  • The biphasic opening of the BBB involves distinct MMPs at different time points post-reperfusion.
  • Current MMP inhibitors offer incomplete protection and can hinder recovery.
  • Developing agents that selectively target pathological BBB opening while preserving repair mechanisms is crucial for treating cerebral ischemia.

More Related Videos

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia09:35

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

Published on: November 15, 2024

An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke12:19

An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke

Published on: March 11, 2018

Related Concept Videos

Cerebral Edema ll: Pathophysiology01:22

Cerebral Edema ll: Pathophysiology

Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...
Cerebral Edema l: Introduction01:19

Cerebral Edema l: Introduction

Cerebral edema is a pathological increase in brain water content that disrupts intracranial pressure regulation and impairs neurological function. Because the cranial vault is rigid, even modest increases in tissue volume can compromise cerebral perfusion, distort neural structures, and initiate secondary injury. Cerebral edema develops through four principal mechanisms: vasogenic, cytotoxic, interstitial, and ionic.Vasogenic EdemaVasogenic edema arises from disruption of the blood–brain...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...
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...
Hemorrhagic Stroke ll: Pathophysiology01:29

Hemorrhagic 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...
Increased Intracranial Pressure ll: Pathophysiology01:29

Increased Intracranial Pressure ll: Pathophysiology

Increased intracranial pressure (ICP) refers to a potentially life-threatening rise in pressure inside the skull. This usually happens when there is a major change in the volume of brain tissue, blood, or cerebrospinal fluid (CSF) — the three components inside the skull. According to the Monro-Kellie doctrine, if the volume of one component increases, the volumes of the other components must decrease to maintain normal pressure. If this does not happen, ICP rises.The process often begins with...