Related Experiment Video

Updated: Aug 16, 2026

A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
09:42

A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model

Published on: June 4, 2021

Tissue plasminogen activator promotes matrix metalloproteinase-9 upregulation after focal cerebral ischemia

Kiyoshi Tsuji1, Toshiaki Aoki, Emiri Tejima

  • 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Stroke
|July 30, 2005
PubMed
Abstract

Insights

Tissue plasminogen activator (tPA) increases matrix metalloproteinase-9 (MMP-9) in ischemic stroke, potentially worsening brain injury. Targeting MMPs alongside tPA may improve stroke treatment outcomes.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Thrombolytic therapy using tissue plasminogen activator (tPA) for ischemic stroke is associated with risks of cerebral hemorrhage and brain injury.
  • These adverse effects may stem from neurovascular proteolysis, particularly mediated by matrix metalloproteinases (MMPs).

Purpose of the Study:

  • To investigate the role of tissue plasminogen activator (tPA) in regulating matrix metalloproteinase-9 (MMP-9) levels during ischemic stroke.
  • To determine if tPA-induced MMP-9 contributes to brain injury and edema following stroke.

Main Methods:

  • Transient focal cerebral ischemia was induced in spontaneously hypertensive rats and in wild-type (WT) and tPA knockout mice.
  • Matrix metalloproteinase-9 (MMP-9) levels, infarct size, and brain edema were assessed using zymography and other histological methods.
  • Pharmacological and genetic approaches, including tPA administration and knockout models, were employed.

Main Results:

  • Exogenous tPA administration amplified MMP-9 levels in ischemic rat brains without altering infarct size.
  • Mice lacking tPA exhibited significantly lower MMP-9 levels, reduced infarct size, and less brain edema compared to WT mice.
  • Administering tPA to tPA knockout mice restored MMP-9 levels to WT levels and exacerbated brain edema.

Conclusions:

  • Tissue plasminogen activator (tPA) demonstrably upregulates brain MMP-9 levels in the context of ischemic stroke in vivo.
  • These findings suggest that MMP-9 is a key mediator of tPA-induced brain injury and edema.
  • Combination therapies targeting MMPs concurrently with tPA may represent a promising strategy to enhance the safety and efficacy of stroke treatment.

More Related Videos

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse08:27

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Published on: July 25, 2011

Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier08:40

Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier

Published on: November 12, 2013

Related Concept Videos

Clot Retraction and Fibrinolysis01:16

Clot 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.
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...
Transient Ischemic Attack l: Introduction01:26

Transient Ischemic Attack l: Introduction

A transient ischemic attack (TIA) is a brief episode of neurological dysfunction caused by a temporary, focal reduction in cerebral blood flow. Although symptoms resemble those of an ischemic stroke, the interruption in perfusion is short-lived and does not cause permanent infarction. TIAs are clinically important because they often serve as early warning events for future stroke.Mechanisms of Transient Cerebral IschemiaTransient cerebral ischemia may arise through several mechanisms. One...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...