Caffeine Exacerbates Postictal Hypoxia
Date
2019-01-07
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Abstract
Background: Postictal hypoxia (PIH) is a stroke-like event that follows seizures and may be responsible for the postictal state. PIH may also be a contributing factor to the development of seizure-induced brain abnormalities and behavioral dysfunction associated with epilepsy. Caffeine is the world’s most popular drug with ~85% of people in the US consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their system during seizures. This pre-clinical study investigated the acute and chronic effects of caffeine on tissue oxygenation pre- and post-seizure. Methods: We utilized the electrical kindling model in rats. A stimulating/recording electrode was placed into the rat ventral hippocampus (CA3), and an oxygen measuring optrode in dorsal hippocampus (CA1). Rats were administered vehicle (saline) or caffeine (5.0, 10.0, or 15.0 mg/kg) intraperitoneally, 30 minutes prior to an elicited seizure. Hippocampal oxygen levels were continually measured post-injection, and post-seizure, until returning to the normoxic range. Further, rats were administered various agonists and antagonists to determine adenosine receptors role in PIH. Lastly, rats were administered a chronic regime of caffeine to determine the long-term effects of caffeine in relation to PIH. Results: Caffeine at high (15. 0mg/kg) doses, caused a significant drop in pre-seizure hippocampal pO2. Following a seizure, caffeine at 10.0mg/kg and 15.0mg/kg, increased the time below the severe hypoxic threshold (10mmHg). Caffeine’s metabolites, paraxanthine, theobromine, and theophylline also increased the time below the severe hypoxic threshold. Adenosine A1 receptor agonist n6-Cyclopentyladenosine caused a significant drop in pre-seizure mean pO2 and increased the area below severe hypoxic threshold. A2A receptor antagonist SCH-58261 caused a significant drop in pre-seizure mean pO2. The A2B receptor, appeared to have no effect on hippocampal pO2 or PIH. Chronic caffeine consumption resulted in an increase in the area below the severe hypoxic threshold on day 15. Rats became tolerant to the drop-in pre-seizure pO2 via chronic consumption but became sensitized to the postictal severe hypoxia effects. Conclusions: Caffeine exacerbates postictal hypoxia; thus, this research hopes to guide future clinical investigations into the effect of caffeine on postictal blood flow and postictal symptomology in persons with epilepsy.
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Keywords
Postictal, Hypoxia, Caffeine, Seizures, Epilepsy
Citation
Phillips, T. J. (2019). Caffeine Exacerbates Postictal Hypoxia (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.