Microglia, Not Leukocytes, in Small Vessel Disease

I investigated inflammatory and vascular pathology in cerebral small vessel disease by integrating human tissue analysis, MRI-linked histopathology and mouse–human disease-model comparison. This work showed that non-amyloid small vessel disease is characterized by microglial activation, focal plasma protein leakage, demyelination and vascular dysfunction without substantial peripheral immune-cell infiltration.

Why the distinction matters

"Neuroinflammation" is often used as if it implied leukocyte entry. This contribution helped refine that interpretation by distinguishing tissue-resident microglial activation and local vascular dysfunction from broad leukocyte-entry models — which changes both the mechanistic picture and the therapeutic target.

The model-selection payoff

It also supported disease-model validation by identifying which mouse models — Notch3 mutant and hypertensive BPH/2J — better recapitulate human white matter and vascular pathology. Most translational failure is decided long before the clinic, at the moment someone picks a model.