Neuroprotective role of transgenic PAF-Acetylhydrolase II in mouse models of focal cerebral ischemia

Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative...

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Bibliographic Details
Published in:Stroke (1970) 2007-03, Vol.38 (3), p.1063-1068
Main Authors: UMEMURA, Kimiko, KATO, Ichiro, ENDO, Shunro, ODA, Masaya, ARAI, Hiroyuki, KINOUCHI, Hiroyuki, HIRAGA, Koichi, HIRASHIMA, Yutaka, ISHII, Yoko, INOUE, Takao, JUNKEN, Aoki, KONO, Nozomu, OYA, Takeshi, HAYASHI, Nakamasa, HAMADA, Hideo
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase - biosynthesis
1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics
1-Alkyl-2-acetylglycerophosphocholine Esterase - therapeutic use
Animals
Biological and medical sciences
Brain Ischemia - enzymology
Brain Ischemia - genetics
Brain Ischemia - prevention & control
Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges
Disease Models, Animal
Female
Fundamental and applied biological sciences. Psychology
Humans
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurology
Neuropharmacology
Neuroprotective agent
Neuroprotective Agents - metabolism
Pharmacology. Drug treatments
Vascular diseases and vascular malformations of the nervous system
Vertebrates: nervous system and sense organs
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Summary:Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P
ISSN:0039-2499
1524-4628
DOI:10.1161/01.STR.0000257981.09329.d2