title: Inhibition of aquaporin-4 significantly increases regional cerebral blood flow.
abstract: The effects of the aquaporin-4 (AQP-4) inhibitor TGN-020 on regional cerebral blood flow (rCBF) was examined in wild-type (WT) and AQP-4 knockout (KO) mice in vivo. Although baseline absolute rCBF of WT and KO mice were equivalent (158.9 ± 17.7 and 155.5 ± 10.4 ml/100 g/min, respectively), TGN-020 produced a significant increase in rCBF compared with saline-treated WT mice (control), reaching a plateau 20 min after administration (118.45 ± 8.13%, P<0.01). TGN-020 showed no effect on KO mice, supporting the concept that the observed increase in rCBF in WT mice was AQP-4 dependent. Administration of acetazolamide (positive control) produced an even greater increase in rCBF in WT compared with TGN-020 and a similar response in KO mice as well, reaching a sustained plateau 5 min after administration (138.50 ± 9.75 and 138.52 ± 9.76%, respectively, P<0.01 compared with baseline or saline-treated control mice). The study demonstrated that AQP-4 plays a role in regulation of rCBF.
authors: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Hironaka
authors: H
authors: Igarashi
authors: Mika
authors: M
authors: Tsujita
authors: Yuji
authors: Y
authors: Suzuki
authors: Ingrid L
authors: IL
authors: Kwee
authors: Tsutomu
authors: T
authors: Nakada
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects; D001784:Blood Gas Analysis; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects; D005260:Female; D007091:Image Processing, Computer-Assisted; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C558003:2-(nicotinamide)-1,3,4-thiadiazole; D051401:Aquaporin 4; D004232:Diuretics; D013830:Thiadiazoles; D009536:Niacinamide; D000086:Acetazolamide