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BJA Advance Access published online on June 11, 2004
British Journal of Anaesthesia, doi:10.1093/bja/aeh188
© 2004 by The Board of Management and Trustees of the British Journal of Anaesthesia
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Accepted March 12, 2004

Laboratory Investigation

Thiopental and isoflurane attenuate the decrease in hippocampal phosphorylated Focal Adhesion Kinase (pp125FAK) content induced by oxygen-glucose deprivation

S. Dahmani 1, A. Tesnière 2, D. Rouelle 3, J.-M. Desmonts 2, J. Mantz 1*

1 Department of Anaesthesia, Bichat University Hospital, 46 rue Henri Huchard, F-75018 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) E9935, Robert Debré University Hospital, 40 Bd Sérurier, F-75019 Paris, France
2 Department of Anaesthesia, Bichat University Hospital, 46 rue Henri Huchard, F-75018 Paris, France
3 Institut National de la Santé et de la Recherche Médicale (INSERM) E9935, Robert Debré University Hospital, 40 Bd Sérurier, F-75019 Paris, France

* To whom correspondence should be addressed. E-mail: jean.mantz{at}bch.ap-hop-paris.fr.


  Abstract

Background. Thiopental and isoflurane exhibit neuroprotective effects against cerebral ischaemia. Here, we hypothesized that oxygen-glucose 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. Rat hippocampal 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 oxygen-glucose deprivation. Thiopental and isoflurane significantly attenuated this phenomenon, possibly via PKC activation.

Keywords: Keywords: anaesthetics volatile, isoflurane; brain, hippocampal slice; complications, aoxia-aglycaemia; model; rat


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