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Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats
Authors Cissé Y, Inoue, Kido H
Received 8 January 2012
Accepted for publication 20 March 2012
Published 22 June 2012 Volume 2012:4 Pages 69—76
DOI https://doi.org/10.2147/JEP.S29769
Review by Single anonymous peer review
Peer reviewer comments 3
Youssouf Cissé,1 Isao Inoue,2 Hiroshi Kido1
1Division of Enzyme Chemistry, 2Division of Molecular Neurobiology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
Background: Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia.
Objective: The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy.
Methods: Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia.
Results: We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations.
Conclusion: Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.
Keywords: influenza A virus, oseltamivir, electroencephalogram, slow oscillations, theta oscillations, hippocampus
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