Hippocampal Oxygen Dynamics During and Following Febrile Seizures
Date
2021-01-22
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Abstract
Objective: Febrile seizures are the most common convulsive event, with anywhere from 2-14% of the population having at least one between 6 months and 5 years of age. Febrile seizures are linked to memory impairments and increased seizure susceptibility. In adults, prolonged seizures resulting from a brain damaging event such as status epilepticus result in hyperoxia. Conversely, brief self-terminating seizures lead to postictal hypoxia. It is currently unknown the dynamic changes in oxygen levels and the mechanisms involved in febrile seizures. Methods: Eight-day-old rat pups were implanted with a hippocampal electrode and oxygen sensing optode. Following surgery rat pups received an immune challenge through 4, once daily injections of lipopolysaccharide. Febrile seizures were then induced using a modified heated dry air model. Before, during and after seizure induction hippocampal local field potentials and oxygen levels were recorded. Separate groups of pups received injections of drugs targeting COX-1, COX-2, L-type calcium channels, CB1 receptors, TRPV1 receptors and adenosine receptors prior to febrile seizure induction. Following febrile seizures, a subset of pups were raised to young adulthood then tested in a novel object recognition paradigm to test learning deficits Seizure thresholds following pentylenetetrazol administration were also tested in adulthood. Results: Febrile seizures result in oxygen dynamics that are related to epileptiform activity. Oxygen following seizures are the same in both male and female rat pups. Oxygen dynamics appear to be linked to seizure length and severity. When a seizure starts there is an initial increase in oxygen, followed by a local oxygen minimum. While oxygen is at the lowest rat pups behaviourally recovery from the seizure, but epileptiform activity in the brain persists. Oxygen then climbs for a second time and does not begin to fall until the epileptiform activity terminates. Calcium channels are involved in seizure behavioural termination with inhibition prolonging recovery while activation decreases time to behavioural recovery without altering epileptiform activity termination. Additionally, inhibiting calcium channels decreases hyperoxia during and following the seizure. Inhibiting COX-1, CB1 and TRPV1 receptors all lead to less hyperoxia postictally. Caffeine had a proconvulsant effect and resulted in less oxygen fluctuations in the hippocampus. A single febrile seizure leads to decreased memory formation but did not alter seizure thresholds in adulthood. Significance: Febrile seizure postictal brain oxygenation does not follow the same pattern or have the same mechanisms as a brief focal seizure or status epilepticus in adults. A single febrile seizure can lead to lasting consequences in memory formation. Brain oxygen dynamics may be an important consideration in the development of treatments for febrile seizures.
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Keywords
Seizures, Postictal Hyperoxia, Febrile Seizure
Citation
Harris, S. (2021). Hippocampal Oxygen Dynamics During and Following Febrile Seizures (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.