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Cadherin peptide‐induced enhancement of blood brain barrier (BBB) permeability
Author(s) -
On Ngoc Hong,
Laksitorini Marlyn,
Kiptoo Paul K,
Siahaan Teruna J,
Miller Donald W
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.668.3
Subject(s) - chemistry , blood–brain barrier , permeability (electromagnetism) , biophysics , rhodamine , peptide , in vivo , peg ratio , pharmacology , fluorescence , biochemistry , medicine , central nervous system , biology , physics , microbiology and biotechnology , finance , quantum mechanics , membrane , economics
Objective To examine the effects of two cadherin peptides, a short linear peptide containing His‐Ala‐Val (HAV) sequence and a cyclic peptide containing the Ala‐Asp‐Thr (cADT) sequence, on BBB integrity. Methods The effects of the HAV and cADT peptides on BBB permeability were examined in Balb/c mice. Blood‐brain barrier permeability was assessed with gadolinium contrast agent (Gad; a small hydrophilic permeability marker), IRdye 800cw PEG (a large hydrophilic permeability marker), and Rhodamine 800 (a P‐gp substrate) under control conditions and following exposure to HAV (1.0–32 mM/kg) or cADT peptides (1mM/kg) using magnetic resonance imaging (MRI) and near infrared fluorescence imaging. Results Mice treated with HAV displayed a dose‐dependent increase in BBB permeability as assessed with Gad enhanced MRI with doses of 1.0 mM/kg having no effect and maximal increases (18‐fold) observed with 32 mM/kg. Increases in BBB permeability were also observed with IRdye 800cw PEG (3‐fold) and Rhodamine 800 (60% increase). The increase in permeability was transient (return to normal within 1 hr). Increases in BBB permeability were also observed with cADT, albeit at lower dose (1.0 mM/kg). Conclusions Cadherin peptides produced a rapid and reversible increase in BBB permeability and the combination of these peptides with therapeutic agents can enhance drug delivery to the brain. Funding: Supported by NSERC and NIH.