Related Experiment Video

Updated: Aug 24, 2026

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse
08:27

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Published on: July 25, 2011

Pathophysiology of focal cerebral ischemia: a therapeutic perspective

Wade S Smith1

  • 1Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143-0114, USA. wssmith@itsa.ucsf.edu

Journal of Vascular and Interventional Radiology : JVIR
|April 23, 2004
PubMed

Insights

Animal models reveal cerebral ischemia pathophysiology, detailing mitochondrial dysfunction and apoptosis. Promising stroke therapies targeting these mechanisms are under investigation despite past clinical trial challenges.

Area of Science:

  • Neuroscience
  • Pathophysiology
  • Stroke Research

Background:

  • Cerebral ischemia pathophysiology is best understood through animal stroke models.
  • Interrupted blood flow rapidly impairs mitochondrial function, ATP generation, and leads to membrane depolarization.
  • This cascade involves increased intracellular calcium and sodium, free radical generation, and apoptosis initiation.

Purpose of the Study:

  • To discuss the pathophysiology of focal cerebral ischemia.
  • To review major human trials in acute stroke therapy based on treatment mechanisms.

Main Methods:

  • Utilized rodent models to elucidate the mechanisms of cerebral ischemia.
  • Reviewed human clinical trials focusing on therapeutic interventions for acute stroke.

Main Results:

  • Identified key steps in ischemic cascade: mitochondrial dysfunction, ion imbalance, oxidative stress, and apoptosis.
  • Highlighted glutamate release as a contributor to neuronal damage.
  • Noted disappointing results in many human acute stroke therapy trials.

Conclusions:

  • Each step in the ischemic cascade presents potential therapeutic intervention points.
  • Despite challenges, promising therapies like hypothermia and free-radical inhibitors are in development.

More Related Videos

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice08:41

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice

Published on: December 29, 2016

Selective and Permanent Occlusion of the Middle Cerebral Artery in Rats: An Experimental Approach for Studying Motor and Spatial Memory Deficits05:44

Selective and Permanent Occlusion of the Middle Cerebral Artery in Rats: An Experimental Approach for Studying Motor and Spatial Memory Deficits

Published on: March 20, 2026

Related Concept Videos

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 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.
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...
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...
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...