Tags

Type your tag names separated by a space and hit enter

Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats.
Brain Res. 2013 Feb 04; 1494:1-8.BR

Abstract

Dexmedetomidine (Dex) has been demonstrated to provide neuroprotection against ischemia/reperfusion (I/R) injury. However, the exact mechanism of this protection remains unknown. Here, we explored the neuroprotective effect of Dex in rats exposed to cerebral I/R-induced by middle cerebral artery occlusion (MCAO) and the role of phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase-3β (GSK-3β) in this protective action. Adult male Sprague-Dawley rats were subjected to MCAO for 90 min followed by reperfusion for 24h and Dex (15 μg/kg, i.v.) was administered immediately after the onset of MCAO. The neurological deficit score, cerebral infarct volume, brain edema, and neuron survival were evaluated at 24h of reperfusion. The effect of Dex on p-Akt, p-ERK1/2 and p-GSK-3β expression in the ischemic hemisphere was assayed by Western blot. Treatment of rats exposed to I/R with Dex caused not only marked reduction in the neurological deficit score, cerebral infarct volume, and brain edema (P <0.01 vs. I/R alone), but also a decrease in neuron death in hippocampal CA1 and cortex (P<0.01 vs. I/R alone). The Dex-induced increment of neuron survival in the ischemic CA1 and cortex was diminished by the PI3K inhibitor LY294002 and the MEK inhibitor U0126. The increasing expressions of p-Akt and p-ERK1/2 induced by Dex in the ischemic hemisphere were markedly inhibited by LY294002 (or wortmannin) and U0126 (or PD98059), respectively. The up-regulation of p-GSK-3β by Dex in the ischemic hemisphere was significantly decreased by both LY294002 (or wortmannin) and U0126 (or PD98059). Our data demonstrated that treatment with Dex reduced cerebral injury in rats exposed to transient focal I/R, and this was mediated by the activation of the PI3K/Akt and ERK1/2 pathways as well the phosphorylation of downstream GSK-3β.

Authors+Show Affiliations

Department of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23219579

Citation

Zhu, Yong-Man, et al. "Both PI3K/Akt and ERK1/2 Pathways Participate in the Protection By Dexmedetomidine Against Transient Focal Cerebral Ischemia/reperfusion Injury in Rats." Brain Research, vol. 1494, 2013, pp. 1-8.
Zhu YM, Wang CC, Chen L, et al. Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. Brain Res. 2013;1494:1-8.
Zhu, Y. M., Wang, C. C., Chen, L., Qian, L. B., Ma, L. L., Yu, J., Zhu, M. H., Wen, C. Y., Yu, L. N., & Yan, M. (2013). Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. Brain Research, 1494, 1-8. https://doi.org/10.1016/j.brainres.2012.11.047
Zhu YM, et al. Both PI3K/Akt and ERK1/2 Pathways Participate in the Protection By Dexmedetomidine Against Transient Focal Cerebral Ischemia/reperfusion Injury in Rats. Brain Res. 2013 Feb 4;1494:1-8. PubMed PMID: 23219579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. AU - Zhu,Yong-Man, AU - Wang,Can-Can, AU - Chen,Long, AU - Qian,Ling-Bo, AU - Ma,Lei-Lei, AU - Yu,Jing, AU - Zhu,Man-Hua, AU - Wen,Chuan-Yun, AU - Yu,Li-Na, AU - Yan,Min, Y1 - 2012/12/05/ PY - 2012/09/10/received PY - 2012/11/26/revised PY - 2012/11/28/accepted PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/7/5/medline SP - 1 EP - 8 JF - Brain research JO - Brain Res. VL - 1494 N2 - Dexmedetomidine (Dex) has been demonstrated to provide neuroprotection against ischemia/reperfusion (I/R) injury. However, the exact mechanism of this protection remains unknown. Here, we explored the neuroprotective effect of Dex in rats exposed to cerebral I/R-induced by middle cerebral artery occlusion (MCAO) and the role of phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase-3β (GSK-3β) in this protective action. Adult male Sprague-Dawley rats were subjected to MCAO for 90 min followed by reperfusion for 24h and Dex (15 μg/kg, i.v.) was administered immediately after the onset of MCAO. The neurological deficit score, cerebral infarct volume, brain edema, and neuron survival were evaluated at 24h of reperfusion. The effect of Dex on p-Akt, p-ERK1/2 and p-GSK-3β expression in the ischemic hemisphere was assayed by Western blot. Treatment of rats exposed to I/R with Dex caused not only marked reduction in the neurological deficit score, cerebral infarct volume, and brain edema (P <0.01 vs. I/R alone), but also a decrease in neuron death in hippocampal CA1 and cortex (P<0.01 vs. I/R alone). The Dex-induced increment of neuron survival in the ischemic CA1 and cortex was diminished by the PI3K inhibitor LY294002 and the MEK inhibitor U0126. The increasing expressions of p-Akt and p-ERK1/2 induced by Dex in the ischemic hemisphere were markedly inhibited by LY294002 (or wortmannin) and U0126 (or PD98059), respectively. The up-regulation of p-GSK-3β by Dex in the ischemic hemisphere was significantly decreased by both LY294002 (or wortmannin) and U0126 (or PD98059). Our data demonstrated that treatment with Dex reduced cerebral injury in rats exposed to transient focal I/R, and this was mediated by the activation of the PI3K/Akt and ERK1/2 pathways as well the phosphorylation of downstream GSK-3β. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/23219579/Both_PI3K/Akt_and_ERK1/2_pathways_participate_in_the_protection_by_dexmedetomidine_against_transient_focal_cerebral_ischemia/reperfusion_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(12)01841-0 DB - PRIME DP - Unbound Medicine ER -