What we're getting WRONG about the "leaky" aging brain | William Banks | 300
Shownotes
Blood-brain barrier as a dynamic interface allowing selective passage of nutrients, peptides, and gut hormones.
TOPICS DISCUSSED:
- Blood-Brain Barrier Structure: Capillary endothelial cells with tight junctions, absent fenestrae, and minimal vesicles create a selective interface; supported by astrocytes and pericytes.
- Crossing Mechanisms: Lipid-soluble small molecules diffuse passively; glucose, amino acids, and regulatory peptides use saturable transporters whose rates vary by need.
- Peptide Transport: Many peptides cross via lipid solubility or specific transporters; rate, not all-or-none presence, determines biological relevance; efflux systems remove some (e.g. certain enkephalins).
- Dynamic Regulation: Transporters for leptin and insulin are modulated by epinephrine, triglycerides, and brain demand; changes occur in aging and Alzheimer’s (reduced glucose uptake, impaired Aβ efflux).
- Circumventricular Organs: Leaky capillary regions allow rapid sampling of blood signals while tanycytes limit spread to surrounding brain tissue.
- Drug Delivery Challenges: Small lipid-soluble drugs, barrier disruption (e.g. focused ultrasound), and “Trojan-horse” strategies each have limitations; intranasal delivery shows rapid brain distribution.
- Peptides & Brain Effects: Gut peptides like GLP-1 analogs, insulin, and ghrelin influence cognition and memory; brain entry predicts central effects.
GUEST: William Banks, MD is a physician-scientist and leading researcher on the blood-brain barrier. He has focused on humoral brain-body communication, peptide transport, and the barrier’s role in health and disease.
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