Related Experiment Video
Updated: Feb 26, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic
Zurab Nadareishvili1,2, Marie Luby1, Richard Leigh1
1Section on Stroke Diagnostics and Therapeutics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Background And Purpose:
Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke.
Methods:
We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan.
Results:
Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011).
Conclusion:
Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke.
Insights
Increased monocyte counts are linked to blood-brain barrier disruption in acute ischemic stroke patients with hyperintense acute reperfusion marker (HARM). This suggests systemic inflammation plays a key role in stroke-related BBB damage.
Area of Science:
- Neurology
- Neuroimaging
- Immunology
Background:
- Blood-brain barrier (BBB) disruption, identified as hyperintense acute reperfusion marker (HARM) on MRI, is linked to matrix metalloproteinase-9 (MMP-9) in acute ischemic stroke.
- Activated leukocytes, particularly monocytes, are primary sources of MMPs, but their direct role in BBB disruption in stroke patients requires further investigation.
Purpose of the Study:
- To investigate the relationship between leukocyte subsets (neutrophils, lymphocytes, monocytes) and BBB disruption (HARM) in acute ischemic stroke patients.
Main Methods:
- Retrospective analysis of prospectively collected data from acute ischemic stroke patients (<12 hours) without reperfusion therapy.
- MRI scans were acquired at baseline, 24 hours, and 5 days, with HARM assessed at 24 hours.
Main Results:
- HARM was detected in 27% of the 33 patients studied.
- HARM-positive patients showed significantly larger baseline perfusion deficits (MTT) and 24-hour DWI infarct growth.
- Significantly higher absolute monocyte counts were observed in HARM-positive patients compared to HARM-negative patients.
Conclusions:
- Elevated monocyte counts correlate with HARM, indicating BBB disruption in acute ischemic stroke.
- These findings highlight the critical role of systemic inflammation in the pathogenesis of BBB disruption following ischemic stroke.
