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Published on: October 17, 2018
Lipopolysaccharide-induced febrile convulsions in the rat: short-term sequelae
James G Heida1, Lysa Boissé, Quentin J Pittman
1Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. jgheida@ucalgary.ca
Insights
Fever can lower the seizure threshold in young rats, potentially leading to febrile convulsions (FCs). This study found no short-term adverse neurological effects from fever-induced seizures in this animal model.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Immunology
Background:
- Febrile convulsions (FCs) are common in children, but their underlying mechanisms and long-term brain development effects are not fully understood.
- Existing research lacks clarity on how fever specifically impacts seizure susceptibility and subsequent neurological outcomes.
Purpose of the Study:
- To investigate the hypothesis that fever can reduce the seizure threshold.
- To develop a reliable animal model for studying febrile convulsions (FCs) using induced fever.
- To examine the short-term neurological sequelae of fever-induced seizures.
Main Methods:
- Utilized 14-day-old rat pups equipped with body-temperature telemetry devices.
- Induced moderate fevers (approx. 1.5°C increase) using lipopolysaccharide (LPS).
- Administered normally subconvulsant doses of kainic acid during fever to induce convulsions, followed by pathological and immunohistochemical analyses.
Main Results:
- Febrile convulsions occurred in approximately 50% of animals when LPS and kainic acid were combined, with minimal mortality.
- Fos immunohistochemistry revealed increased immunoreactivity in seizure-related brain regions in animals experiencing FCs.
- No significant pathological brain changes were observed 72 hours after induced FCs.
Conclusions:
- A neuroimmune challenge accompanied by fever demonstrably lowers the seizure threshold.
- The induced febrile convulsions in this model did not result in observable short-term adverse effects on the brain.
- This fever-induced FC model offers a valuable tool for further research into the role of fever and its mediators in seizure genesis.
Purpose:
Febrile convulsions (FCs) occur in children as a result of fever. The mechanisms involved in the genesis of FCs and their long-term consequences on brain development remain unclear. We have developed a model of FC, by using fever as a parameter, to test the hypothesis that fever can lower seizure threshold and to examine the neurologic sequelae of FCs.
Methods:
Fourteen-day-old rat pups equipped with body-temperature telemetry devices exhibited approximately 1.5 degrees C fevers after lipopolysaccharide (Escherichia coli, 200 microg/kg). During such fevers, concurrently administered doses of kainic acid that are normally subconvulsant were used to induce convulsions with fever. Animals were then killed at varying times for pathological and immunohistochemical studies.
Results:
The pairing of lipopolysaccharide and subconvulsant kainic acid resulted in convulsions in approximately 50% of febrile animals, with very low mortality. To study the neural correlates of these FCs, we used fos immunohistochemistry and found that animals with FCs had fos-positive immunoreactivity in brain regions involved in seizures. After a period of 72 h, we also examined brains for pathologic changes and found no differences among our groups.
Conclusions:
Our data indicate that a neuroimmune challenge and its accompanying fever reduce the seizure threshold. Furthermore, the FCs induced by fever in this model do not have short-term adverse effects on the brain. In addition, this model, by incorporating physiologic fever, may be useful for examining the role of fever and its constituent mediators in the genesis of FCs.
