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Updated: Mar 2, 2026
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute
Natalia S Rost1, Pedro Cougo1, Svetlana Lorenzano1,2
11 J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.
Insights
White matter changes in acute ischemic stroke (AIS) patients are linked to blood-brain barrier (BBB) leakage and white matter damage. These MRI markers may predict stroke outcomes.
Area of Science:
- Neurology
- Radiology
- Vascular Biology
Background:
- Acute ischemic stroke (AIS) involves complex pathophysiology affecting brain tissue.
- Blood-brain barrier (BBB) integrity and white matter integrity are crucial for neurological function.
- Understanding the interplay between BBB permeability and white matter microstructural integrity in AIS is vital for predicting outcomes.
Purpose of the Study:
- To investigate the relationship between BBB permeability and white matter microstructural integrity in AIS patients.
- To explore the impact of these factors on long-term functional outcomes.
- To identify potential MRI markers for predicting stroke outcomes.
Main Methods:
- 184 AIS subjects underwent perfusion-weighted MRI (PWI) within 9 hours of symptom onset.
- Calculated white matter hyperintensity (WMH), infarct, and PWI lesion volumes.
- Measured BBB leakage (K2 coefficient) and mean diffusivity in normal-appearing white matter (NAWM), alongside MMP-2 levels and NIHSS/mRS scores.
Main Results:
- Higher BBB leakage (K2) and diffusivity correlated with older age, elevated MMP-2, greater stroke severity (NIHSS), and worse functional outcomes (mRS).
- White matter hyperintensity (WMH) volume was significantly associated with increased BBB permeability and abnormal diffusivity in contralesional NAWM.
- These findings suggest a link between WMH severity and diffuse cerebral microvascular dysfunction.
Conclusions:
- WMH severity in AIS patients is associated with increased BBB permeability and impaired white matter microstructure.
- MRI markers of BBB permeability and white matter integrity may serve as predictors of stroke-related tissue damage and functional recovery.
- Further research utilizing these markers could enhance the prediction of long-term post-stroke outcomes.
