Neuroprotective role of dexmedetomidine pretreatment in cerebral ischemia injury via ADRA2A‑mediated phosphorylation of ERK1/2 in adult rats

Shi,Yanyan; Peng,Xiao‑Hong; Li,Xia; Luo,Gao‑Ping; Wu,Ming‑Fu

doi:10.3892/etm.2018.6878

Neuroprotective role of dexmedetomidine pretreatment in cerebral ischemia injury via ADRA2A‑mediated phosphorylation of ERK1/2 in adult rats

Authors:
- Yanyan Shi
- Xiao‑Hong Peng
- Xia Li
- Gao‑Ping Luo
- Ming‑Fu Wu
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Affiliations: Department of Anesthesia, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: October 18, 2018 https://doi.org/10.3892/etm.2018.6878
Pages: 5201-5209
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuroprotective effects of dexmedetomidine (Dex) have been reported in various models of brain injury. However, to our knowledge, the neuroprotective mechanism of Dex pretreatment in rats remains unknown. The aim of the present study was to detect the expression of the α2A adrenergic receptor (ADRA2A) in focal ischemic brain tissues and to investigate the protective role and corresponding mechanism of Dex pretreatment in cerebral ischemia in rats. A hypoxia/reoxygenation (H/R) cell model in primary cultured astrocytes and a focal cerebral ischemia/reperfusion (I/R) model in adult rats were used. The expression of ADRA2A and extracellular signal‑regulated kinases 1 and 2 (ERK1/2) in the primary cultured astrocytes and rat brain ischemic tissues was detected in the different conditions prior to and following Dex pretreatment using western blotting. The H/R model of primary cultured astrocytes and the focal cerebral I/R model in adult rats were successfully constructed. Under the normal oxygen conditions, 500 ng/ml Dex pretreatment increased the expression of ADRA2A and phosphorylated (p)‑ERK1/2 in the astrocytes compared with in the control group. Hypoxic culture for 6 h and then reoxygenation for 24 h decreased the levels of p‑ERK1/2 in the astrocytes compared with those in control group. This decrease was prevented by Dex pretreatment for 3 h. The hypoxic culture and then reoxygenation increased the expression of ADRA2A. Similarly, compared with those prior to Dex treatment, the levels of ADRA2A and p‑ERK1/2 in the brain ischemic tissues following Dex treatment were increased. The levels of ADRA2A and p‑ERK1/2 were 0.72±0.23 and 0.66±0.25 following Dex treatment, compared with 0.76±0.22 and 0.31±0.18, respectively, prior to Dex treatment. The effect of Dex pretreatment increasing p‑ERK1/2 expression was attenuated by AG1478 pretreatment. In summary, Dex appeared to promote phosphorylation of ERK1/2 in astrocytes under H/R. As a specific agonist of ADRA2A, Dex may activate phosphorylation of ERK1/2 via ADRA2A in astrocytes. Thus, the neuroprotective role of Dex pretreatment against cerebral ischemic injury may function via ADRA2A‑mediated phosphorylation of ERK1/2.

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