Related Experiment Video
Updated: Jun 19, 2025
Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid
Published on: April 7, 2023
Increased Permeability of the Blood-Brain Barrier in a Diabetic Mouse Model (Lepr/ Mice)
Musaad A Alshammari1, Abdulaziz O Alshehri2, Faleh Alqahtani1
1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Abstract:
Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Lepr/ mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Lepr/ animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Lepr untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Lepr/ control mice than in all remaining groups. Identifying the factors that increase the BBB in Lepr/ mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.
Insights
Type 2 Diabetes Mellitus (T2DM) impairs the blood-brain barrier (BBB) integrity, increasing its permeability. This study reveals BBB molecular and functional changes in a T2DM mouse model, linking T2DM to brain complications.
Area of Science:
- Neuroscience
- Endocrinology
- Vascular Biology
Background:
- Type 2 Diabetes Mellitus (T2DM) is associated with cognitive impairment and neurodegenerative diseases.
- Alterations in the blood-brain barrier (BBB) microvascular and macrovascular environment are implicated in T2DM-related brain complications.
Purpose of the Study:
- To investigate the functional and molecular integrity of the BBB in a T2DM animal model.
- To identify factors contributing to BBB changes in T2DM.
Main Methods:
- Utilized RT-PCR, functional pharmacokinetic studies with sodium fluorescein (NaFL), and confocal microscopy.
- Examined leptin receptor-deficient mutant mice (Lepr-/-) as a T2DM model.
- Compared BBB markers and permeability in T2DM mice versus wild-type controls.
Main Results:
- Observed dysregulation of BBB-related markers (VCAM-1, ICAM-1, MMP-9, S100b) in Lepr-/- mice.
- Found significantly increased brain concentration and permeability of NaFL in untreated Lepr-/- mice.
- Demonstrated higher NaFL permeability in Lepr-/- control mice compared to other groups.
Conclusions:
- T2DM significantly impacts BBB integrity, evidenced by molecular marker dysregulation and increased permeability.
- Findings provide insights into T2DM-associated brain pathologies and fill knowledge gaps in this research area.
- Understanding BBB changes in T2DM is crucial for addressing related neurological complications.
More Related Videos
09:35An In Vivo Blood-brain Barrier Permeability Assay in Mice Using Fluorescently Labeled Tracers
Published on: February 26, 2018
07:22Assessment of Blood-brain Barrier Permeability by Intravenous Infusion of FITC-labeled Albumin in a Mouse Model of Neurodegenerative Disease
Published on: November 8, 2017
