title: Cognitive dysfunction induced by chronic cerebral hypoperfusion in a rat model associated with arteriovenous malformations.
abstract: The relationship between chronic cerebral hypoperfusion and cognitive function has not been completely delineated. In the present studies, we developed an experimental model associated with arteriovenous malformation to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neuropathological changes. The rat model was established by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein and the ipsilateral common carotid artery, followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Age-matched rats comprised a control group. Three months after surgery, cognitive functions were evaluated by the Morris water maze and hippocampal long-term potentiation (LTP). Neuropathological changes were examined using light and electron microscopic techniques. We found that both learning capacity and spatial memory were significantly impaired in rats with chronic cerebral hypoperfusion concomitant with LTP inhibition and neurodegeneration in the hippocampal CA1 region of model rats compared with control rats. In addition, model rats showed a decrease at the protein level of cyclic AMP response element binding (CREB) phosphorylation in hippocampal tissues. Therefore, cognitive impairment caused by chronic cerebral hypoperfusion associated with arteriovenous malformations may be partially explained by the neurodegeneration and reduction of CREB phosphorylation in rat hippocampus.
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji University, Shanghai, China. haijiandoc@yahoo.com.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Hai
authors.forename: Jue-Feng
authors.initials: JF
authors.lastname: Wan
authors.forename: Qi
authors.initials: Q
authors.lastname: Lin
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001164:Arteriovenous Fistula / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D016923:Cell Death; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004594:Electrophysiology; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein