Caffeine Exacerbates Postictal Hypoxia

Neuroscience. 2019 Dec 1:422:32-43. doi: 10.1016/j.neuroscience.2019.09.025. Epub 2019 Oct 31.

Abstract

A stroke-like event follows seizures which may be responsible for the postictal state and 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 USA consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their body and brain during seizures. This preclinical study investigated the effects of acute caffeine on local hippocampal tissue oxygenation pre and post seizure. We continuously measured local oxygen levels in the CA1 region of the hippocampus and utilized the electrical kindling model in rats. Rats were acutely administered either caffeine, or one of its metabolites, or agonists and antagonists at adenosine sub-receptor types or ryanodine receptors prior to the elicitation of seizures. Acute caffeine administration caused a significant drop in pre-seizure hippocampal pO2. Following a seizure, caffeine, as well as two of its metabolites paraxanthine, and theophylline, increased the time below the severe hypoxic threshold (10 mmHg). Likewise, the specific A2A receptor antagonist, SCH-58261, mimicked caffeine by causing a significant drop in pre-seizure pO2 and the area and time below the severe hypoxic threshold. Moreover, the A2A receptor agonist, CGS-21680 was able to prevent the effect of both caffeine and SCH-58261 adding further evidence that caffeine is likely acting through the A2A receptor. Clinical tracking and investigations are needed to determine the effect of caffeine on postictal symptomology and blood flow in persons with epilepsy.

Keywords: caffeine; hypoperfusion; hypoxia; postictal; seizure; vasoconstriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Animals
  • CA1 Region, Hippocampal / metabolism
  • Caffeine / adverse effects*
  • Caffeine / analogs & derivatives
  • Caffeine / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Hypoxia / complications
  • Hypoxia / physiopathology*
  • Kindling, Neurologic / drug effects
  • Male
  • Oxygen / metabolism
  • Phenethylamines / pharmacology
  • Pyrimidines / antagonists & inhibitors
  • Pyrimidines / pharmacology
  • Rats
  • Receptors, Adenosine A2 / drug effects
  • Receptors, Adenosine A2 / physiology*
  • Seizures / complications
  • Seizures / physiopathology*
  • Triazoles / antagonists & inhibitors
  • Triazoles / pharmacology

Substances

  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Phenethylamines
  • Pyrimidines
  • Receptors, Adenosine A2
  • Triazoles
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Caffeine
  • Adenosine
  • Oxygen

Grants and funding