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Updated: Feb 15, 2026

An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke
Published on: March 11, 2018
Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping
Marina Y Khodanovich1, Alena A Kisel1, Andrey E Akulov1,2
11 Laboratory of Neurobiology, Tomsk State University, Tomsk, Russian Federation.
Abstract:
A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups ( n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.
Insights
Fast macromolecular proton fraction (MPF) mapping accurately quantifies demyelination after stroke. This MRI technique shows strong correlation with histological markers, validating MPF as a key biomarker for ischemic stroke research.
Area of Science:
- Neuroimaging
- Stroke Research
- Demyelination
Background:
- Ischemic stroke causes demyelination, impacting neurological function.
- Accurate quantification of demyelination is crucial for understanding stroke pathology and recovery.
- Existing MRI methods require validation against histological markers.
Purpose of the Study:
- To validate fast macromolecular proton fraction (MPF) mapping as an imaging biomarker for demyelination in a rat stroke model.
- To compare MPF with other quantitative MRI parameters and histological markers of brain injury.
- To assess the correlation between MPF and demyelination markers over time post-stroke.
Main Methods:
- Utilized transient middle cerebral artery occlusion (MCAO) in rats.
- Acquired quantitative MRI data, including MPF, T1, T2, proton density, and ADC.
- Compared MRI parameters with histological stains (Luxol Fast Blue, Bielschowsky) and immunohistochemistry (NeuN, Iba1) at 1, 3, and 10 days post-MCAO.
Main Results:
- MPF and Luxol Fast Blue (LFB) optical density were significantly reduced in the ischemic lesion compared to the contralateral hemisphere.
- MPF and LFB optical density showed a strong correlation (R=0.81), validating MPF's ability to detect demyelination.
- Incorporating T2 into regression analysis improved MPF-LFB agreement by correcting for edema.
Conclusions:
- Fast macromolecular proton fraction (MPF) mapping is a validated imaging biomarker for demyelination in ischemic stroke.
- MPF provides a reliable, non-invasive method for assessing demyelination severity.
- This technique holds potential for clinical applications in stroke diagnosis and monitoring.
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