Neuroprotective and neurotoxic properties of the ‘inert’ gas, xenon

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Neuroprotective and neurotoxic properties of the ‘inert’ gas, xenon D. Ma, S. Wilhelm, M. Maze, N.P. Franks British Journal of Anaesthesia Volume 89, Issue 5, Pages 739-746 (November 2002) DOI: 10.1093/bja/aef258 Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 1 Representative coronal sections showing half of the arcuate nucleus of the hypothalamus stained for c-Fos positive immunoreactivity. (a) Three hours after subcutaneous injection of NMA (100 mg kg−1) the c-Fos positive neurons are easily visualised by dense black staining. (b) For animals injected with NMA but also exposed to 75% xenon there was a marked reduction in the number of c-Fos positive neurons. The scale bar represents 100 μm and the third ventricle is marked V3. British Journal of Anaesthesia 2002 89, 739-746DOI: (10.1093/bja/aef258) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 2 Mean number of NMA-induced c-Fos positive neurones in the arcuate nucleus of the hypothalamus is greatly reduced by xenon. Data are mean (sem). **P<0.01 relative to NMA treatment alone. The inset shows data from control animals injected with saline and the lack of effect when xenon is applied alone (i.e. in the absence of NMA). The inset also presents results from a positive control showing that MK801 (0.5 mg kg−1) in the presence of NMA reduces the number of c-Fos positive neurones to control levels while having no effect per se. British Journal of Anaesthesia 2002 89, 739-746DOI: (10.1093/bja/aef258) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 3 Nitrous oxide and ketamine but not xenon are neurotoxic. Representative coronal sections showing the posterior cingulate and retrosplenial cortices stained for c-Fos positive immunoreactivity. (a) Control. (b) Ninety minutes after exposure to 75% xenon. (c) Ninety minutes after exposure to 75% nitrous oxide. (d) Ninety minutes after s.c. injection of ketamine 100 mg kg−1. The scale bar represents 100 μm. British Journal of Anaesthesia 2002 89, 739-746DOI: (10.1093/bja/aef258) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 4 Concentration or dose–response effects of xenon, nitrous oxide, and ketamine on the number of c-Fos positive neurons in the posterior cingulate and retrosplenial cortices. Results are means (sem). *P<0.05; **P<0.01 relative to control. The data for MK801 (0.5 mg kg−1), a prototypical NMDA receptor antagonist are presented as a positive control. British Journal of Anaesthesia 2002 89, 739-746DOI: (10.1093/bja/aef258) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 5 Haloperidol, a dopamine D2 receptor antagonist, blocks nitrous oxide and ketamine-induced neurotoxicity. Data show the number of c-Fos positive neurones in the posterior cingulate and retrosplenial cortices following exposure to 75% nitrous oxide or s.c. injection of ketamine (50 mg kg−1) compared with control. Results are means (sem). **P<0.01 relative to control. British Journal of Anaesthesia 2002 89, 739-746DOI: (10.1093/bja/aef258) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions