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Dose-Dependent Influence of Sevoflurane Anesthesia on Neuronal Survival and Cognitive Outcome After Transient Forebrain Ischemia in Sprague-Dawley Rats

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Abstract

Background

Volatile anesthetics reduce postischemic neurohistopathological injury and improve neurological outcome in various animal models. However, the isoflurane concentrations above 1 minimum alveolar concentration (MAC) have been associated with reduced neuronal survival and impaired functional outcome. The aim of this study was to evaluate if 1.8 MAC sevoflurane alters postischemic neuronal survival and neurologic outcome compared with 0.45 MAC sevoflurane.

Methods

In this study, 20 fasted male Sprague-Dawley rats were randomly assigned to treatment groups with 1 or 4 vol.% sevoflurane end-tidal concentration. Cerebral ischemia was induced by bilateral carotid artery occlusion and hemorrhagic hypotension (BCAO). The cognitive outcome was assessed after 7 days using the object recognition test. Animals were then re-anesthetized and brains were removed for neurohistopathological analysis of the hippocampus (CA1) and cortex using hematoxylin-eosin staining.

Results

Physiologic parameters were not different between both the treatment groups. The number of viable neurons (median [Q1, Q3]) in the CA1 region on postischemic day 7 was increased after high-dose sevoflurane compared with low-dose sevoflurane (1645 [453, 1825] vs. 3222 [2920, 3993] neurons/ROI, P < 0.05). Results of the object recognition test were not different between both the treatment groups.

Conclusions

Postischemic neuronal survival was increased with 1.8 MAC compared with 0.45 MAC sevoflurane. Therefore, experimental models of cerebral ischemia should account for neuroprotective effects of sevoflurane with increasing concentrations. To ensure minimal interference of sevoflurane on neuronal survival, a low inspired concentration should be used and fluctuations in the depth of anesthesia should be limited.

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Acknowledgments

The authors gratefully acknowledge the excellent technical assistance provided by Frida Kornes (Technician, Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany) and for the statistical advice provided by Dr. Antje Jahn-Eimermacher (Dipl. Math.). The data in this study form a part of a doctoral thesis submitted by Thorsten Wolf (Medical Student, Medical Center of the Johannes Gutenberg-University, Mainz, Germany) to the Medical Faculty, Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

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Authors and Affiliations

  1. Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany

    Irina Lasarzik, Rüdiger R. Noppens, Thorsten Wolf, Clara Luh, Christian Werner, Kristin Engelhard & Serge C. Thal

  2. Department of Neuropathology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Henrike Bauer

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  1. Irina Lasarzik
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  2. Rüdiger R. Noppens
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Correspondence to Serge C. Thal.

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Irina Lasarzik and Rüdiger R. Noppens are considered as equal first authors.

Kristin Engelhard and Serge C. Thal are considered as equal co-senior authors.

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Lasarzik, I., Noppens, R.R., Wolf, T. et al. Dose-Dependent Influence of Sevoflurane Anesthesia on Neuronal Survival and Cognitive Outcome After Transient Forebrain Ischemia in Sprague-Dawley Rats. Neurocrit Care 15, 577–584 (2011). https://doi.org/10.1007/s12028-011-9562-3

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