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Related Experiment Video

Updated: Nov 4, 2025

A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model

A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model

Published on: June 4, 2021

Targeting Parthanatos in Ischemic Stroke.

Raymond C Koehler¹, Valina L Dawson^2,3,4,5, Ted M Dawson^2,3,4,6

¹Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD, United States.

Frontiers in Neurology

|May 24, 2021

Summary

This summary is machine-generated.

Parthanatos, a cell death pathway, is implicated in stroke. PARP inhibitors show neuroprotective potential by reducing cell death and neuroinflammation, suggesting therapeutic promise for stroke treatment.

Keywords:

cerebral ischemia middle cerebral artery occlusion neuroinflammation parthanatos poly(ADP ribose) polymerase stroke

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Area of Science:

Neuroscience
Cell Biology
Pharmacology

Background:

Parthanatos is a cell death pathway triggered by DNA damage and poly(ADP-ribose) polymerase (PARP) overactivation.
This pathway involves mitochondrial release of apoptosis-inducing factor, leading to nuclear DNA degradation and cell death.

Purpose of the Study:

To review the literature on the role of parthanatos in stroke models.
To evaluate the neuroprotective potential of PARP inhibitors in stroke.

Main Methods:

Literature review of 24 publications from 13 laboratories.
Analysis of studies using PARP inhibitors (19 studies) or PARP1-null mice (7 studies) in middle cerebral artery occlusion (MCAO) models.
Examination of studies in young male and female rodents.

Main Results:

Strong evidence supports parthanatos in young male rodents after MCAO, with a therapeutic window of 4-6 hours.
Evidence for parthanatos in young female rodents is mixed.
PARP inhibitors also reduce neuroinflammation, limit blood-brain barrier damage, and suppress matrix metaloproteinase-9 release.

Conclusions:

The literature strongly supports PARP inhibitors as neuroprotective agents for stroke.
Third-generation PARP inhibitors, with favorable safety profiles in oncology, could be repurposed for stroke treatment.
Further evaluation in aged animals and those with comorbidities is crucial before clinical trials.