Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats

Intracerebroventricular Application of Dexmedetomidine Produces Antinociception and Does not Cause Neurotoxicity in Rats

“…In previous studies, with intrathecal administration of higher doses of the alpha 2 agonist clonidine, no neurotoxic (34) found that intravenous administration of 15 µg/ kg dexmedetomidine protected the brain against focal cerebral ischaemia/reperfusion in rats after middle cerebral artery occlusion. They concluded that dexmedetomidine decreased the neurological deficit score, brain edema, cerebral infarct volume, and neuronal death.…”

Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

“…Dex is known to be protective against IR in various organs including the kidneys, lung, brain and liver [14,[40][41][42]. The cardiac preconditioning effect of…”

“…However, the exact mechanisms by which Dex attenuates IR injury are still being elucidated. Dex can protect against renal, lung and brain IR through the regulation of the JAK/STAT, TLR4/MyD88/MAPK and RISK pathways, respectively [14,41,45]. Regarding the heart, Okada et al described that Dex protected the myocardium against global IR.…”

“…The mechanism by which it protects may be organspecific. The mechanisms reported to be involved in organ protection include: a) modulation of cell death by apoptosis [11]; b) activation of cell survival kinases [12,13]; and, c) modulation of the inflammatory response and oxidative stress [14]. Few studies have addressed the pharmacological mechanism involved in Dex-dependent cardioprotection [15,16].…”

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

“…The α 2 -AR-focal adhesion kinase-Src-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) (23,24), and the imidazoline I 1 receptor-extracellular signal-regulated kinase 1/2 (ERK1/2)-mitochondrial ATP-sensitive K + channel pathways (25) are involved in the preconditioning and postconditioning effects of DEX against hippocampal oxygen and glucose deprivation-induced injury (26). Treatment with DEX reduces cerebral injury in rats exposed to transient focal I/R, which is mediated by the activation of the PI3K/Akt and ERK1/2 pathways, as well as the phosphorylation of downstream glycogen synthase kinase 3 (27). In addition, DEX attenuates mouse hippocampal CA1 long-term potentiation.…”