BJA Advance Access originally published online on June 11, 2004
British Journal of Anaesthesia 2004 93(2):270-274; doi:10.1093/bja/aeh188
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2004
Thiopental and isoflurane attenuate the decrease in hippocampal phosphorylated Focal Adhesion Kinase (pp125FAK) content induced by oxygenglucose deprivation
1 Department of Anaesthesia, Bichat University Hospital, 46 rue Henri Huchard, F-75018 Paris, France. 2 Institut National de la Santé et de la Recherche Médicale (INSERM) E9935, Robert Debré University Hospital, 40 Bd Sérurier, F-75019 Paris, France
* Corresponding author. E-mail: jean.mantz{at}bch.ap-hop-paris.fr
Background. Thiopental and isoflurane exhibit neuroprotective effects against cerebral ischaemia. Here, we hypothesized that oxygenglucose deprivation decreases the ATP-dependent phosphorylation process of Focal Adhesion Kinase (pp125FAK, a functionally important non-receptor tyrosine kinase), and that this phenomenon is attenuated by thiopental and isoflurane.
Methods. Rathippocampal slices were subjected to an anoxic-aglycaemic (or physiologic, control) challenge followed by 3-h reperfusion, and treated with various concentrations of thiopental and isoflurane. PP125FAK phosphorylation was measured by immunoblotting. Neuronal death was assessed by immunostaining with bis-benzimide.
Results. Significant neuronal death was detected after 30 min (but not 10) of anoxia-aglycaemia (40 (4) vs 14 (5)% of control, P<0.05). At 30 min, phosphorylated pp125FAK content was significantly decreased by anoxic glucose-free conditions (55 (27)% of control, P<0.05). This effect was markedly attenuated by thiopental (10 and 100 µM) and isoflurane (1 and 2%). Under control conditions, thiopental (1, 10, and 100 µM) and isoflurane (0.5, 1, and 2%) increased pp125FAK phosphorylation in a concentration-related fashion. This effect was blocked by chelerythrin and bisindolylmaleimide I and IX (10 µM, three structurally distinct inhibitors of protein kinase C, PKC) but not the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (10 µM).
Conclusion. Phosphorylated pp125FAK content was markedly decreased in hippocampal slices subjected to oxygenglucose deprivation. Thiopental and isoflurane significantly attenuated this phenomenon, possibly via PKC activation.