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Updated: Aug 7, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Intrinsic activated microglia map to the peri-infarct zone in the subacute phase of ischemic stroke
Christopher J S Price1, Dechao Wang, David K Menon
1Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK. cp252@medschl.cam.ac.uk
Background And Purpose:
Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally and spatially. In vivo studies in stroke patients have relied on positron emission tomography and (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. In this study we sought to establish temporal and spatial patterns of microglial activation in ischemic stroke with particular emphasis on a defined peri-infarct zone.
Methods:
Using this technique, we studied carotid territory ischemic stroke patients in 3 time windows up to 30 days after ictus. Controls were studied in a single session. [11C](R)-PK11195 injection was followed by 3-dimensional acquisition over 60 minutes. Cerebral blood volume (CBV) was measured afterward with the use of standard C15O paradigms. Analysis employed the reference tissue model in which ipsilateral cerebellum was used to generate parametric binding potential maps corrected for CBV. Data were coregistered to T1-based MRI. Using control data to identify 99% confidence limits, a region of interest analysis was applied to identify significant binding in core infarction, contralateral hemisphere, and within a defined peri-infarct zone.
Results:
Four patients (mean age, 66 years) were imaged across 9 sessions. Four age-matched controls were studied. Within this model, ipsilateral cerebellum was validated as a reference tissue. With the use of control-derived confidence limits and correction for CBV, significant binding potential rises were identified beyond 72 hours and extending to 30 days in core infarction, contralateral hemisphere, and peri-infarct zone.
Conclusions:
In ischemic stroke patients, minimal activation of microglia is seen before 72 hours. Beyond this, binding potential rises in core infarction, peri-infarct zone, and contralateral hemisphere to 30 days. This may represent a therapeutic opportunity that extends beyond time windows traditionally reserved for neuroprotection.
Insights
Microglial activation in ischemic stroke patients is minimal before 72 hours. Beyond this, it increases in the core infarction, peri-infarct zone, and contralateral hemisphere for up to 30 days.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Microglial activation is a key component of neuroinflammation following ischemic stroke.
- Previous in vivo studies in stroke patients utilized positron emission tomography with (R)-PK11195 to assess microglial activation.
- Understanding the temporal and spatial patterns of microglial activation is crucial for stroke research.
Purpose of the Study:
- To establish temporal and spatial patterns of microglial activation in ischemic stroke patients.
- To specifically investigate microglial activation in the peri-infarct zone.
- To utilize positron emission tomography with [11C](R)-PK11195 for in vivo imaging.
Main Methods:
- Carotid territory ischemic stroke patients were studied in three time windows up to 30 days post-ictus.
- Positron emission tomography with [11C](R)-PK11195 was used to measure binding potential, with cerebral blood volume (CBV) correction.
- Data were coregistered to MRI, and analysis involved a reference tissue model using the ipsilateral cerebellum.
Main Results:
- Significant binding potential increases were observed beyond 72 hours and extended to 30 days post-stroke.
- Elevated binding potential was detected in the core infarction, peri-infarct zone, and contralateral hemisphere.
- The ipsilateral cerebellum was validated as a suitable reference tissue for analysis.
Conclusions:
- Microglial activation in ischemic stroke patients is minimal before 72 hours.
- Activation persists and increases in multiple brain regions up to 30 days post-ictus.
- This extended timeframe suggests potential therapeutic opportunities beyond traditional neuroprotection windows.
