title: Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus.
abstract: Intracerebral hemorrhage (ICH) is a severe type of stroke causing neurological dysfunction with a high mortality rate. Dexmedetomidine is an agonist for α2‑adrenoreceptors with sedative, anxiolytic, analgesic and anesthetic effects. In the present study, we investigated the effects of dexmedetomidine on short‑term and spatial learning memory, as well as its effects on apoptosis following the induction of ICH in rats. A rat model of IHC was created by an injection of collagenase into the hippocampus using a stereotaxic instrument. Dexmedetomidine was administered intraperitoneally daily for 14 consecutive days, commencing 1 day after the induction of ICH. The step‑down avoidance test for short‑term memory and the radial 8‑arm maze test for spatial learning memory were conducted. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end-labeling (TUNEL) assay, immunohistochemistry for caspase‑3, and western blot analysis for Bcl‑2, Bax, Bid and caspase-3 expression were performed for the detection of apoptosis in the hippocampus. Western blot analysis for the brain‑derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was also performed for the detection of cell survival in the hippocampus. The induction of ICH deteriorated short‑term and spatial learning memory, increased apoptosis and suppressed BDNF and TrkB expression in the hippocampus. Treatment with dexmedetomidine ameliorated the ICH‑induced impairment of short‑term and spatial learning memory by suppressing apoptosis and enhancing BDNF and TrkB expression. In the normal rats, dexmedetomidine exerted no significant effects on memory function and apoptosis. The present results suggest the possibility that dexmedetomidine may be used as a therapeutic agent for the conservation of memory function in stroke patients.
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Lakkyong
authors.initials: L
authors.lastname: Hwang
authors.forename: In-Young
authors.initials: IY
authors.lastname: Choi
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Il-Gyu
authors.initials: IG
authors.lastname: Ko
authors.forename: Mal-Soon
authors.initials: MS
authors.lastname: Shin
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jun-Jang
authors.initials: JJ
authors.lastname: Jin
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Chung
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Yi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D053938:DNA Fragmentation / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008570:Memory, Short-Term / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020927:Dexmedetomidine; D020813:Receptor, trkB; D053148:Caspase 3