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A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
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Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke
Michael K Schuhmann1, Alexander M Kollikowski2, Alexander G März2
1Department of Neurology, University Hospital Würzburg, Germany.
Brain, Behavior, & Immunity - Health
|September 30, 2021
Summary
This study found higher levels of damage-associated molecular patterns (DAMPs), including HMGB1 and S100A8/A9, within the ischemic brain compartment of stroke patients. These elevated DAMPs correlate with brain damage and immune cell infiltration, linking cell death to stroke inflammation.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Acute cerebral ischemia triggers immune responses contributing to stroke progression.
- Damage-associated molecular patterns (DAMPs) like HMGB1 and S100A8/A9 are released by dying cells, activating innate immunity.
Purpose of the Study:
- To directly measure local DAMPs concentrations and immune cell infiltration within the ischemic cerebral compartment in human stroke patients.
- To investigate the relationship between local DAMPs and stroke severity and inflammation.
Main Methods:
- Microcatheter sampling from the occluded cerebral artery core before mechanical thrombectomy.
- Comparison of local ischemic samples with systemic control samples from the internal carotid artery post-recanalization.
Main Results:
- Increased local concentrations of high-mobility group box 1 protein (HMGB1) by 33% and S100A8/A9 by 8% within the ischemic compartment.
- Local HMGB1 levels correlated with infarct size on admission.
- Local HMGB1 and S100A8/A9 concentrations were associated with leukocyte infiltration into the occluded compartment.
Conclusions:
- First direct human evidence of elevated DAMPs in a sealed ischemic cerebral vascular compartment.
- Establishes a direct pathophysiological link between ischemia-induced cell death and stroke-related inflammation.

