Increased cortical extracellular adenosine correlates with seizure termination

Area of Science:

• Neuroscience
• Biochemistry
• Epilepsy Research

Background:

• Seizures are defined by electrographic features, but neurotransmitter dynamics during seizures are poorly understood.
• Adenosine shows promise in terminating seizures, evidenced by animal models and human microdialysis studies.
• Previous human studies had temporal limitations in measuring adenosine during seizures.

Purpose of the Study:

• To test the hypothesis that extracellular adenosine concentrations increase during seizure termination.
• To investigate periictal adenosine dynamics using high-temporal-resolution electrochemistry.
• To correlate adenosine levels with electrographic seizure events in real-time.

Main Methods:

• Utilized an acute cortical epilepsy model in swine (n=45) and studied 10 human epilepsy patients during intraoperative electrocorticography (ECoG).
• Employed Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry for adenosine measurement.
• Collected simultaneous ECoG and electrochemical data to capture periictal neurotransmitter changes.

Main Results:

• Demonstrated an average adenosine increase of 260% prior to electrographic seizure termination in swine.
• Observed adenosine elevation occurring seconds before seizure termination using both amperometry (7.5 ± 16.9 s) and FSCV (2.6 ± 11.2 s).
• Confirmed similar adenosine elevation preceding seizure termination in a human patient using FSCV.

Conclusions:

• Simultaneous ECoG and electrochemical recordings support the hypothesis of rising adenosine levels before seizure termination.
• Findings suggest adenosine may be intrinsically responsible for seizure termination.
• Future intraoperative WINCS-based FSCV recordings can further elucidate the adenosine-seizure relationship.