Related Experiment Video
Updated: May 15, 2026
07:34
Induction of Acute Ischemic Stroke in Mice Using the Distal Middle Artery Occlusion Technique
Published on: December 15, 2023
PGJ(2) provides prolonged CNS stroke protection by reducing white matter edema
James D Nicholson1, Adam C Puche, Yan Guo
1Department of Ophthalmology and Visual Sciences, University of Maryland-Baltimore School of Medicine, Baltimore, Maryland, United States of America.
Plos One
|January 4, 2013
Summary
15-deoxy-Δ(12,14)-prostaglandin J2 (PGJ(2)) significantly protects the central nervous system (CNS) white matter from ischemic injury. PGJ(2) reduces inflammation and improves neuronal survival, offering a potential treatment for CNS infarcts.
Area of Science:
- Neuroscience
- Pharmacology
- Pathology
Background:
- Central nervous system (CNS) white matter injury lacks effective clinical treatments.
- Inflammatory pathways, particularly NFκB signaling, exacerbate early ischemic damage, leading to progressive lesions.
- 15-deoxy-Δ(12,14)-prostaglandin J2 (PGJ(2)), a PGD(2) metabolite analog, shows potential for mitigating such injury.
Purpose of the Study:
- To evaluate the neuroprotective effects and underlying mechanisms of PGJ(2) in a rodent model of white matter ischemia.
- To determine if PGJ(2) can improve neuronal survival and vascular function post-ischemic insult.
- To assess the safety and toxicity profile of PGJ(2) in the optic nerve.
Main Methods:
- Rodent anterior ischemic optic neuropathy (rAION) model was used to simulate white matter ischemia.
- PGJ(2) was administered systemically, either acutely or 5 hours post-insult.
- Neuroprotection was assessed via stereology for neuronal survival, capillary vascular analysis for perfusion, and evaluation of NFκB signaling pathways. Optic nerve structure, function, and cellular/gene expression were analyzed for toxicity.
Main Results:
- Systemic PGJ(2) administration, even 5 hours post-insult, significantly improved neuronal survival 30 days after infarction.
- PGJ(2) enhanced perfusion by day 1 post-insult, likely by reducing tissue edema.
- The compound reduced NFκB signaling by inhibiting p65 nuclear localization and downstream inflammatory gene expression.
- No structural, functional, cellular, or gene expression toxicity was observed in the optic nerve.
Conclusions:
- PGJ(2) demonstrates significant neuroprotective effects in a white matter ischemia model.
- Its mechanism involves the suppression of NFκB-driven inflammation.
- PGJ(2) offers a promising therapeutic candidate for CNS infarcts, potentially with a wider therapeutic window than currently considered.
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.
01:29Hemorrhagic 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...
01:22Cerebral 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...
01:17Hemorrhagic Stroke l: Introduction
A hemorrhagic stroke is an acute neurological event that occurs when a weakened cerebral blood vessel ruptures, allowing blood to accumulate within or around the brain. The sudden release of blood forms a focal hematoma that increases intracranial pressure, displaces neural tissue, and can obstruct cerebrospinal fluid pathways. These effects may be compounded by intraventricular extension of the hemorrhage, cerebral edema, or compression of adjacent structures, all of which contribute to...
01:19Cerebral 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...