Rat model of influenza-associated encephalopathy (IAE): studies of electroencephalogram (EEG) in vivo

• Published in: Neuroscience 2010-02, Vol.165 (4), p.1127-1137
• Main Authors: Cissé, Y, Wang, S, Inoue, I, Kido, H
• Format: Article
• Language: English
• Subjects: Adenylate cyclase; Adrenergic alpha-Agonists - pharmacology; Anesthetics, Dissociative - pharmacology; Animals; Biological and medical sciences; Brain - drug effects; Brain - physiopathology; Brain Diseases - blood; Brain Diseases - etiology; Brain Diseases - physiopathology; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; cytokines; Disease Models, Animal; EEG; Electroencephalography; Fever - physiopathology; Fundamental and applied biological sciences. Psychology; hippocampus; Hippocampus - drug effects; Hippocampus - physiopathology; hyperthermia; influenza; Influenza A Virus, H1N1 Subtype; Interleukin-6 - blood; Ketamine - pharmacology; Male; Neurology; Orthomyxoviridae Infections - blood; Orthomyxoviridae Infections - complications; Orthomyxoviridae Infections - physiopathology; Rats; Rats, Wistar; theta activity; Theta Rhythm - drug effects; Time Factors; Vertebrates: nervous system and sense organs; Xylazine - pharmacology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.10.062

Abstract Influenza-associated encephalopathy (IAE) is characterized by severe neurological complications during high-grade fever with high morbidity and mortality in children. The major neurological complications during high-grade fever include convulsive seizures, loss of consciousness, neuropsychiatric behavior (hallucination, meaningless speech, disorientation, laughing alone); high voltage amplitude slow waves and the occurrence of theta oscillation are depicted on the electroencephalogram (EEG) in the IAE patients. At the early phase of the disease, the cytokines levels increase in severe cases. To understand the neuronal properties in the CNS leading to these neurological complications in IAE patients, we recorded EEG signals from the hippocampus and cortex of rats infected with influenza A/WSN/33 H1N1 virus (IAV) strain. Abnormal EEG activities were observed in all infected rats under anesthesia, including high voltage EEG burst amplitude and increased EEG spikes in the early phase (8 h–day 2) of infection, and these increases at the early phase were in parallel with a significant increase level of interleukin-6 (IL-6) in the serum. When the infected rats were heat-stressed by elevating the rat body core temperature to 39–41 °C, these abnormal EEG activities were enhanced, and the oscillation pattern shifted in most of rats from slow bursting waves (