Isoflurane Neuroprotection in Hypoxic Hippocampal Slice Cultures Involves Increases in Intracellular Ca2+and Mitogen-activated Protein Kinases

Abstract

Isoflurane stimulates the phosphorylation of survival signaling proteins in hypoxic neurons. The mechanism involves a moderate increase in [Ca2+]i from release of Ca from inositol triphosphate receptor-dependent intracellular stores. The increase in [Ca2+]i sets in motion signaling via Ras and the MAP kinase p42/44 pathway and the antiapoptotic factor Akt. Isoflurane neuroprotection thus involves intracellular signaling well known to suppress both excitotoxic and apoptotic/delayed cell death.

p38 Mitogen-Activated Protein Kinase Contributes to Adenosine A1Receptor-Mediated Synaptic Depression in Area CA1 of the Rat Hippocampus

“…Another form of ischemic preconditioning in the brain can be elicited by volatile anesthetics (Kapinya et al, 2002;Zhao and Zuo, 2004;Bickler et al, 2005;Gray et al, 2005), which requires the activation of A 1 receptors (Liu et al, 2006) and p38 MAPK (Zheng and Zuo, 2004). In the present study, we showed that the inhibitory actions of adenosine A 1 receptors, but not other inhibitory receptors such as GABA B receptors, were attenuated by p38 MAPK inhibitors.…”

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase

“…Previous evidence indicates that U0126 could block the neuroprotection induced by isoflurane in hippocampal slice cultures [24] , suggesting that the neuroprotection of isoflurane is induced through activating the MEK-ERK1/2 signal pathway. However, this neuroprotection effect was not induced by APC.…”

“…By phosphorylating specific serine and threonine residues in cellular targets, they affect gene expression, mitosis, cytokinesis, metabolism, and cell death. Many studies demonstrate that modulations of extracellular signal-regulated protein kinases (MEK-ERK1/2, ERK1/2 MAPK) and p38 MAPK activities either by ischemia or by pharmacological agents are important in the genesis of the cytoprotective phenotype [22][23][24][25][26] . To date, no data are available with respect to the role of MAPKs in APC.…”

Isoflurane-Induced Caspase-3 Activation Is Dependent on Cytosolic Calcium and Can Be Attenuated by Memantine

“…vation and to cause apoptosis (Matsuoka et -Faberowski et al, 2001;de Klaver et al, 2002;Kawaguchi et al, 2004;Wise-Faberowski et al, 2004;Gray et al, 2005). This difference could be attributable to the use of different cell lines (e.g., rat cardiac cells vs human neural cells) or differences in duration and concentration of isoflurane exposure (Xie et al, 2006a,b).…”