Neurochemical investigation of multiple locally induced seizures using microdialysis sampling: Epilepsy effects on glutamate release

Abstract

The objective of this study was to develop an in vivo model for locally induced epilepsy. Epilepsy is a prominent neurological disorder that affects millions of people worldwide. Patients may experience either global seizures, affecting the entire brain, or focal seizures, affecting only one brain region. The majority of epileptic patients experience focal seizures but they go undiagnosed because such seizures can be difficult to detect. To better understand the effects of focal epilepsy on the neurochemistry of a brain region with high seizure diathesis, an animal model for locally induced seizures in the hippocampus was developed. In this model, two seizure events were chemically induced by administering the epileptogenic agent, 3-mercaptopropionic acid (3-MPA), to the hippocampus to disturb the balance between excitatory and inhibitory neurotransmitters in the brain. Microdialysis was used for local delivery of 3-MPA as well as for collection of dialysate for neurochemical analyses. Two periods of seizures separated by varying inter-seizure recovery times were employed, and changes in the release of the excitatory transmitter, glutamate, were measured. Significant differences in glutamate release were observed between the first and second seizure episodes. Diminished glutamate biosynthesis, enhanced glutamate re-uptake, and/or neuronal death were considered possible causes of the attenuated glutamate release during the second seizure episode. Biochemical measurements were indicative that a combination of these factors led to the attenuation in glutamate release.