title: Endogenous pituitary adenylate cyclase activating polypeptide is involved in suppression of edema in the ischemic brain.
abstract: Pituitary adenylate cyclase activating polypeptide is a pleiotropic neuropeptide. We previously showed that heterozygous PACAP gene knockout (PACAP(+/-)) mice had larger infarct volumes and worse neurological scores after middle cerebral artery occlusion (MCAO). However, the relationship between endogenous PACAP levels and edema in the ischemic brain has not yet been evaluated. In this study, the formation of edema in the ischemic brain as well as cerebral blood flow was compared between PACAP(+/-) and wild-type (PACAP(+/+)) mice. The amount of brain edema was calculated by subtracting the contralateral volume from the ipsilateral volume 24 h after permanent MCAO. PACAP(+/-) mice showed significantly greater brain edema than PACAP(+/+) mice. To investigate the effects of endogenous PACAP on blood flow during ischemia, cerebral blood flow in the ipsilateral and the contralateral cortices was compared between PACAP(+/-) and PACAP(+/+) mice for 25 min after ischemia. With a two-dimensional laser Doppler perfusion imaging system, the blood flow in the ipsilateral and contralateral cortices was shown to be similar in PACAP(+/-) and PACAP(+/+) mice during ischemia. These results suggest that endogenous PACAP suppresses the formation of edema in the ischemic brain.
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yofu
authors.forename: Kenji
authors.initials: K
authors.lastname: Dohi
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Mori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D002540:Cerebral Cortex / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000378:metabolism*; D012039:Regional Blood Flow / Q000235:genetics; D013997:Time Factors; D018608:Ultrasonography, Doppler / Q000379:methods
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide