title: Dexmedetomidine alleviates cerebral ischemia-induced short-term memory impairment by inhibiting the expression of apoptosis-related molecules in the hippocampus of gerbils.
abstract: Cerebral ischemia results from cerebrovascular occlusion, which leads to neuronal cell death and eventually causes neurological impairments. Dexmedetomidine is a potent and highly selective α2-adrenoreceptor agonist with actions such as sedation, anxiolysis, analgesia and anesthetic-sparing effects. We investigated the effect of dexmedetomidine on apoptosis in the hippocampus after transient global ischemia in gerbils. Transient global ischemia was induced by ligation of both common carotid arteries. Dexmedetomidine was administrated intraperitoneally at three respective doses (0.1, 1 and 10 µg/kg) once per day for 14 consecutive days beginning a day after surgery. Short-term memory was assessed by use of a step-down avoidance task. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, immunohistochemistry for caspase-3, and western blot analysis of Bcl-2-associated X protein, B-cell lymphoma 2, Bid, cytochromec, apoptotic protease activating factor-1 and caspase-9 in the hippocampus. Induction of global ischemia deteriorated short-term memory by enhancing the expression of apoptosis-related molecules in the hippocampus. Treatment with dexmedetomidine suppressed the expression of apoptosis-related molecules under ischemic conditions, resulting in short-term memory improvement. Under normal conditions, dexmedetomidine exerted no significant effect on apoptosis in the hippocampus. The present results suggest that the α2-adrenoceptor agonist dexmedetomidine may be a useful therapeutic agent for the treatment of ischemic brain diseases.
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: In-Young
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Lakkyong
authors.initials: L
authors.lastname: Hwang
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Jun-Jang
authors.initials: JJ
authors.lastname: Jin
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Il-Gyu
authors.initials: IG
authors.lastname: Ko
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Mal-Soon
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Key-Moon
authors.initials: KM
authors.lastname: Shin
authors.affiliation: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, Kyung Hee University College of Medicine, Seoul 130-872, Republic of Korea.
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, Kyung Hee University College of Medicine, Seoul 130-872, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kangdong Kyung Hee Hospital, Kyung Hee University College of Medicine, Seoul 134-727, Republic of Korea.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Yi
keywords: apoptosis; dexmedetomidine; gerbils; short-term memory; transient global ischemia; α2-adrenergic receptor