The study shows that delta sleep‑inducing peptide (DSIP) and several of its modified versions can cross the blood‑cerebrospinal fluid barrier in dogs when given intravenously. How much gets into the brain fluid depends mainly on three things: how high the blood level is, how long the peptide stays in the blood (half‑life), and how oily (lipophilic) the molecule is. Protein binding and size didn’t matter much.

Delta sleep-inducing peptide (DSIP) or one of four DSIP analogs (desTrp-DSIP, D-Ala3-DSIP, D-Ala4-DSIP, D-Ala4-DSIP-NH2), was injected IV into dogs. Samples of cerebrospinal fluid (CSF) from the posterior fossa and blood were collected simultaneously at 2, 5, 10, 20, 30, 45, and 60 min after injection and concentrations of DSIP-like material measured by radioimmunoassay (RIA). The increase in peptide concentration in the CSF correlated significantly with the increase in plasma concentration, with plasma half-life, and with peptide lipophilicity, but not with the degree of plasma protein binding or with molecular weight. An even better correlation occurred when the three factors that correlated independently were combined into a single parameter (r = 0.813, p less than 0.00005). These results demonstrate that peptides can significantly penetrate the blood-CSF barrier of the dog. For DSIP and its analogs, the degree of penetration into the CSF is highly dependent on parameters such as the level of peptide in the plasma, plasma half-life, and the lipophilicity of the peptide.