Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus

Hwang,Lakkyong; Choi,In-Young; Kim,Sung-Eun; Ko,Il-Gyu; Shin,Mal-Soon; Kim,Chang-Ju; Kim,Sang-Hoon; Jin,Jun-Jang; Chung,Jun-Young; Yi,Jae-Woo

doi:10.3892/ijmm.2013.1301

Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus

Authors:
- Lakkyong Hwang
- In-Young Choi
- Sung-Eun Kim
- Il-Gyu Ko
- Mal-Soon Shin
- Chang-Ju Kim
- Sang-Hoon Kim
- Jun-Jang Jin
- Jun-Young Chung
- Jae-Woo Yi
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Affiliations: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea, Department of Physical Education, Graduate School of Education, Sang Myung University, Seoul 110-743, Republic of Korea, Department of Physical Activity Design, College of Science, Hanseo University, Seosan 356-706, Republic of Korea, Department of Anesthesiology and Pain Medicine, Gangdong Kyung Hee Hospital, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea
Published online on: March 13, 2013 https://doi.org/10.3892/ijmm.2013.1301
Pages: 1047-1056

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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.

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