Table 2.

Human studies presenting data relevant for understanding PACAP transport across the blood-brain barrier

Grände, 2013 [8]	Investigate effect of PACAP27 and PACAP38 on human and rat arteries.	In vitro myograph of human MCA and in vitro pressurized arteriography of rat MCA.	PACAP38 and PACAP27 had effect after abluminal but not luminal application in the rat. Both PACAPs had effect on the human MCA abluminal.	Luminal application of PACAP to the human MCA was not done in this study.
Amin, 2012 [4]	Investigate effect of i.v. PACAP38 infusion on MCA and MMA in healthy volunteers.	MR-angiography before and after iv infusion of PACAP38.	Large dilation of the MMA but no change of the MCA caliber.	MMA dilation was long-lasting (110 min), while MCA remained unchanged.
Amin, 2014 [5]	Investigate effect of i.v. PACAP38 infusion on MCA and MMA in migraine patients.	MR-angiography before and after iv infusion of PACAP38.	Large dilation of the MMA but no change of the MCA caliber.	MMA dilation was long-lasting (120 min), while MCA remained unchanged. Median time from infusion start to onset of migraine was 4.5 h.

PTS-6 protein transport system-6, BBB blood-brain barrier, PACAP pituitary adenylate cyclase-activating polypeptide, BSCB blood-spinal cord barrier, MCA middle cerebral artery, ICR outbred mouse, SAMP8 a mouse model of Alzheimer, where altered BBB to other substances is known, LPS lipopolysaccharide (used to disrupt the BBB), TAT a peptide derived from the human immunodeficiency virus 1, MMA middle meningeal artery