title: Effect of propofol post-treatment on blood-brain barrier integrity and cerebral edema after transient cerebral ischemia in rats.
abstract: Although propofol has been reported to offer neuroprotection against cerebral ischemia injury, its impact on cerebral edema following ischemia is not clear. The objective of this investigation is to evaluate the effects of propofol post-treatment on blood-brain barrier (BBB) integrity and cerebral edema after transient cerebral ischemia and its mechanism of action, focusing on modulation of aquaporins (AQPs), matrix metalloproteinases (MMPs), and hypoxia inducible factor (HIF)-1α. Cerebral ischemia was induced in male Sprague-Dawley rats (n = 78) by occlusion of the right middle cerebral artery for 1 h. For post-treatment with propofol, 1 mg kg(-1) min(-1) of propofol was administered for 1 h from the start of reperfusion. Nineteen rats undergoing sham surgery were also included in the investigation. Edema and BBB integrity were assessed by quantification of cerebral water content and extravasation of Evans blue, respectively, following 24 h of reperfusion. In addition, the expression of AQP-1, AQP-4, MMP-2, and MMP-9 was determined 24 h after reperfusion and the expression of HIF-1α was determined 8 h after reperfusion. Propofol post-treatment significantly reduced cerebral edema (P < 0.05) and BBB disruption (P < 0.05) compared with the saline-treated control. The expression of AQP-1, AQP-4, MMP-2, and MMP-9 at 24 h and of HIF-1α at 8 h following ischemia/reperfusion was significantly suppressed in the propofol post-treatment group (P < 0.05). Propofol post-treatment attenuated cerebral edema after transient cerebral ischemia, in association with reduced expression of AQP-1, AQP-4, MMP-2, and MMP-9. The decreased expression of AQPs and MMPs after propofol post-treatment might result from suppression of HIF-1α expression.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Hui Song
authors.initials: HS
authors.lastname: Cui
authors.forename: Seo Kyung
authors.initials: SK
authors.lastname: Shin
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Bon-Nyeo
authors.initials: BN
authors.lastname: Koo
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis; D051401:Aquaporin 4 / Q000096:biosynthesis; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051398:Aquaporin 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D015742:Propofol