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Updated: Nov 24, 2025
Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Imaging epileptic foci in mouse models via a low-density lipoprotein receptor-related protein-1 targeting strategy
Cong Wang1, Jianping Zhang2, Shaoli Song3
1Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China; National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China.
Background:
In the setting of drug-resistant epilepsy (DRE), the success of surgery depends on the ability to accurately locate the epileptic foci to be resected or disconnected. However, the epileptic foci in a considerable percentage of the DRE patients cannot be adequately localised. This warrants the need for a reliable imaging strategy to identify the "concealed" epileptic regions.
Methods:
Brain specimens from DRE patients and kainate-induced epileptic mouse models were immuno-stained to evaluate the integrity of the blood-brain barrier (BBB). The expression of low-density lipoprotein receptor-related protein-1 (LRP1) in the epileptic region of DRE patients and kainate models was studied by immunofluorescence. A micellar-based LRP1-targeted paramagnetic probe (Gd3+-LP) was developed and its ability to define the epileptic foci was investigated by magnetic resonance imaging (MRI).
Findings:
The integrity of the BBB in the epileptic region of DRE patients and kainate mouse models were demonstrated. LRP1 expression levels in the epileptic foci of DRE patients and kainate models were 1.70-2.38 and 2.32-3.97 folds higher than in the control brain tissues, respectively. In vivo MRI demonstrated that Gd3+-LP offered 1.68 times higher (P < 0.05) T1-weighted intensity enhancement in the ipsilateral hippocampus of chronic kainite models than the control probe without LRP1 specificity.
Interpretation:
The expression of LRP1 is up-regulated in vascular endothelium, activated glia in both DRE patients and kainate models. LRP1-targeted imaging strategy may provide an alternative strategy to define the "concealed" epileptic foci by overcoming the intact BBB.
Funding:
This work was supported by the National Natural Science Foundation, Shanghai Science and Technology Committee, Shanghai Municipal Science and Technology, Shanghai Municipal Health and Family Planning Commission and the National Postdoctoral Program for Innovative Talents.
Insights
A novel imaging probe targets LRP1 to visualize hidden epilepsy foci in drug-resistant epilepsy (DRE) patients. This approach overcomes the intact blood-brain barrier (BBB), offering a new strategy for surgical planning.
Area of Science:
- Neuroscience
- Medical Imaging
- Epileptology
Background:
- Accurate localization of epileptic foci is crucial for successful epilepsy surgery.
- A significant percentage of drug-resistant epilepsy (DRE) patients have poorly localized seizure origins.
- There is a need for advanced imaging techniques to identify these
Purpose of the Study:
- To develop and evaluate an LRP1-targeted imaging probe for visualizing concealed epileptic foci.
- To assess the integrity of the blood-brain barrier (BBB) in epileptic regions.
- To investigate the expression of LRP1 in DRE and epilepsy models.
Main Methods:
- Immunohistochemistry on brain specimens from DRE patients and kainate-induced mouse models.
- Evaluation of blood-brain barrier (BBB) integrity.
- Development of a micellar-based LRP1-targeted paramagnetic probe (Gd3+-LP).
- Magnetic resonance imaging (MRI) to assess probe efficacy.
Main Results:
- The BBB integrity was maintained in epileptic regions of DRE patients and mouse models.
- LRP1 expression was significantly elevated (1.70-3.97 fold) in epileptic foci compared to controls.
- The LRP1-targeted probe (Gd3+-LP) showed significantly higher T1-weighted intensity enhancement in MRI compared to a non-targeted probe.
Conclusions:
- LRP1 is upregulated in the vascular endothelium and activated glia within epileptic foci.
- An LRP1-targeted imaging strategy can potentially visualize "concealed" epileptic regions by crossing the intact BBB.
- This approach offers a promising alternative for improving surgical outcomes in DRE.
