Endothelial negative surface charge areas and blood-brain barrier function

Area of Science:

• Neuroscience
• Vascular Biology
• Biochemistry

Background:

• The blood-brain barrier (BBB) maintains brain homeostasis by restricting molecular passage.
• Negative surface charge on brain endothelial cells is crucial for BBB integrity.
• Polycations can interact with and potentially alter BBB function.

Purpose of the Study:

• To investigate the effect of the polycation protamine on blood-brain barrier function in vivo.
• To determine the role of protamine's positive charge and other properties in BBB disruption.
• To explore mechanisms of BBB opening induced by protamine.

Main Methods:

• Intracarotid infusion of protamine in awake rats.
• Assessment of blood-brain barrier permeability using albumin and inulin as tracers.
• Comparison of protamine's effects with those of lysine, another polycation.

Main Results:

• High doses of protamine significantly increased blood-brain barrier permeability to albumin and inulin.
• Protamine's positive charge was identified as a key factor in disrupting the BBB.
• Protamine exhibited additional BBB-disrupting properties beyond charge, potentially cytotoxic.

Conclusions:

• Protamine can effectively impair blood-brain barrier function.
• Both the positive charge and other cytotoxic effects of protamine contribute to BBB opening.
• Further research is needed to understand if BBB opening occurs at specific membrane locations lacking negative charge.