Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7

Area of Science:

• Neuroscience
• Pharmacology
• Cell Biology

Background:

• The blood-brain barrier (BBB) restricts the passage of substances into the brain.
• Understanding BBB permeability is crucial for drug delivery and neurological research.
• Bradykinin agonists are being investigated for their potential to modulate BBB function.

Purpose of the Study:

• To investigate the route of lanthanum (LaCl3) transport across the cerebral endothelium.
• To determine the effect of RMP-7, a bradykinin agonist, on BBB permeability.
• To elucidate the mechanism by which RMP-7 alters endothelial tight junctions.

Main Methods:

• Balb C mice were infused with LaCl3, with or without RMP-7.
• Electron microscopy was used to visualize and quantify LaCl3 penetration.
• The patency of endothelial junctions and tracer movement into basal lamina and perivascular spaces were analyzed.

Main Results:

• RMP-7 significantly increased the penetration of LaCl3 across endothelial tight junctions compared to controls.
• Lanthanum tracer spread into the basal lamina and perivascular spaces in RMP-7 treated mice.
• Evidence suggested a paracellular route of exudation, with minimal evidence of transcytosis.

Conclusions:

• RMP-7 opens the blood-brain barrier by increasing the permeability of endothelial tight junctions.
• The primary route of LaCl3 passage across the RMP-7-treated BBB is paracellular.
• These findings provide insights into BBB regulation and potential strategies for therapeutic interventions.