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Published on: November 19, 2020
Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI
Marilena Marinescu1, Fabien Chauveau, Anne Durand
1UMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1, 28 avenue du Doyen LEPINE, 69677, Bron, France.
Objectives:
This study sought to evaluate whether the therapeutic effects of an anti-inflammatory drug such as minocycline could be monitored by serial ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI in experimental stroke.
Methods:
Mice received a three-dose minocycline treatment (n = 12) or vehicle (n = 12) after permanent middle cerebral artery occlusion. USPIOs were administered 5 h post-surgery. MRI was performed before, 24 h and 48 h post-USPIO administration. MRI endpoints were the extent of signal abnormalities on R2 maps (=1/T2) and quantitative R2 changes over time (∆R2). Post-mortem brains were prepared either for immunohistology (n = 16) or for iron dosage (n = 8).
Results:
As expected, treatment with minocycline significantly reduced infarct size, blood-brain barrier permeability and F4/80 immunostaining for microglia/macrophages. Areas of R2 maps > 35 ms(-1) also appeared significantly decreased in minocycline-treated mice (ANOVA for repeated measures, P = 0.017). There was a fair correlation between these areas and the amount of iron in the brain (R(2) = 0.69, P = 0.010), but no significant difference in ∆R2 was found between the two groups.
Conclusions:
This study showed that the extent of signal abnormalities on R2 maps can be used as a surrogate marker to detect minocycline effects in a murine experimental model of stroke.
Insights
Minocycline treatment reduced stroke damage in mice. Ultrasmall superparamagnetic iron oxide-enhanced MRI detected these therapeutic effects by monitoring signal abnormalities on R2 maps, serving as a potential biomarker.
Area of Science:
- Neuroimaging
- Pharmacology
- Stroke Research
Background:
- Experimental stroke models are crucial for evaluating therapeutic interventions.
- Minocycline, an anti-inflammatory drug, shows promise in neuroprotection.
- Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI offers potential for monitoring treatment effects.
Purpose of the Study:
- To assess if serial USPIO-enhanced MRI can monitor the therapeutic effects of minocycline in an experimental stroke model.
- To investigate the correlation between MRI findings and histological/biochemical markers of inflammation and iron deposition.
Main Methods:
- Mice with induced middle cerebral artery occlusion received either minocycline or vehicle treatment.
- Ultrasmall superparamagnetic iron oxide (USPIO) particles were administered, followed by serial MRI scans at different time points.
- MRI endpoints included signal abnormalities on R2 maps and quantitative R2 changes; post-mortem analysis involved immunohistology and iron quantification.
Main Results:
- Minocycline treatment significantly reduced infarct size, blood-brain barrier permeability, and microglial/macrophage infiltration.
- Areas with signal abnormalities on R2 maps (>35 ms⁻¹) were significantly decreased in minocycline-treated mice.
- A correlation was observed between R2 map abnormalities and brain iron content, though no significant difference in quantitative R2 changes was found between groups.
Conclusions:
- Signal abnormalities on R2 maps, assessed via USPIO-enhanced MRI, can serve as a surrogate marker for detecting minocycline's therapeutic effects in experimental stroke.
- This imaging approach may facilitate non-invasive monitoring of anti-inflammatory drug efficacy in stroke models.
