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Supplementary Material Abbreviations ACN acetonitrile aCSF artificial cerebrospinal fluid AngIV angiotensin IV ANOVA analysis of variance AUC area under the curve BBB blood-brain barrier Cl int average intrinsic clearance C max concentration in plasma extrapolated to time zero (C 0 ) dihexa N -hexanoic-Tyr-Ile-(6) amino-hexanoic amide DMSO dimethyl sulfoxide HGF hepatocyte growth factor HPLC high-pressure liquid chromatography logP log transformation of the octanol/water partition ratio and measure of hydrophilicity mEPSC miniature excitatory postsynaptic currents Nle 1 -AngIV Nle-Tyr-Ile-His-Pro-Phe PBS phosphate-buffered saline P eff predicted effective human jejunal permeability PIPES piperazine- N , N -bis(2-ethanesulfonic acid) t 1/2 terminal elimination rate constant V d volume of distribution VGLUT1 vesicular glutamate transporter 1 Authorship Contributions Participated in research design: McCoy, Benoist, Wright, Harding, Appleyard, Wayman, Kawas

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