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Cerebral Microbleeds and Their Association With Inflammation and Blood-Brain Barrier Leakage in Small Vessel Disease
Lupei Cai1, Daniel J Tozer1, Hugh S Markus1
1Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, United Kingdom.
Background:
How cerebral microbleeds (CMBs) are formed, and how they cause tissue damage is not fully understood, but it has been suggested they are associated with inflammation, and they could also be related to increased blood-brain barrier (BBB) leakage. We investigated the relationship of CMBs with inflammation and BBB leakage in cerebral small vessel disease, and in particular, whether these 2 processes were increased in the vicinity of CMBs.
Methods:
In 54 patients with sporadic cerebral small vessel disease presenting with lacunar stroke, we simultaneously assessed microglial activation using the positron emission tomography ligand [11C]PK11195 and BBB leakage using dynamic contrast enhanced magnetic resonance imaging, on a positron emission tomography-magnetic resonance imaging system. To assess local inflammation and BBB leakage, 3 one-voxel concentric shells were generated around each CMB on susceptibility-weighted imaging and resampled to positron emission tomography and T1 mapping images, respectively. In these 3 shells, we calculated the mean of PK11195 nondisplaceable binding potential (BPND) as a marker of microglial activation, as well as the mean influx rate as a marker of BBB leakage. In addition, 93 blood biomarkers related to cardiovascular disease, inflammation, and endothelial activation were measured to quantify systemic inflammation.
Results:
No significant associations were found between the number of CMBs and the measures for microglial activation (β=2.6×10-5, P=0.050) and BBB leakage (β=-0.0001, P=0.400) in the white matter. There was no difference in measures of microglial activation (P=0.403) or BBB leakage (P=0.423) across the 3 shells surrounding the CMBs. Furthermore, after correcting for multiple comparisons, no associations were observed between systemic inflammation biomarkers and the number of CMBs.
Conclusions:
We found no evidence that CMBs are associated with either microglial activation assessed by [11]CPK11195 positron emission tomography or BBB leakage assessed by dynamic contrast enhanced magnetic resonance imaging, either globally or locally, in sporadic cerebral small vessel disease. There was also no association with markers of systemic inflammation.
Insights
Cerebral microbleeds (CMBs) are not associated with inflammation or blood-brain barrier (BBB) leakage in small vessel disease. This study found no link between CMBs and microglial activation or BBB permeability, even locally around the bleeds.
Area of Science:
- Neuroscience
- Radiology
- Pathology
Background:
- Cerebral microbleeds (CMBs) are linked to inflammation and blood-brain barrier (BBB) leakage, but mechanisms remain unclear.
- Investigating the relationship between CMBs, inflammation, and BBB integrity is crucial for understanding cerebral small vessel disease (CSVD).
Purpose of the Study:
- To investigate the association of CMBs with local and systemic inflammation and BBB leakage in patients with sporadic CSVD.
- To determine if inflammation and BBB leakage are increased in the vicinity of CMBs.
Main Methods:
- 54 patients with sporadic CSVD and lacunar stroke underwent simultaneous assessment of microglial activation using [11C]PK11195 PET and BBB leakage using dynamic contrast-enhanced MRI.
- Concentric shells around CMBs were used to assess local microglial activation (BPND) and BBB leakage (influx rate).
- Blood biomarkers were analyzed to quantify systemic inflammation.
Main Results:
- No significant association was found between the number of CMBs and microglial activation or BBB leakage in white matter.
- No differences in microglial activation or BBB leakage were observed across shells surrounding CMBs.
- No associations were found between systemic inflammation biomarkers and the number of CMBs after correction for multiple comparisons.
Conclusions:
- This study found no evidence that CMBs are associated with microglial activation or BBB leakage, either globally or locally, in sporadic CSVD.
- The findings suggest that inflammation and BBB leakage may not be direct consequences of CMBs in this patient group.
- Further research is needed to fully elucidate the pathophysiology of CMBs and their impact on brain tissue.
