Skip to Main content Skip to Navigation
Journal articles

Epileptogenic action of caffeine during anoxia in the neonatal rat hippocampus.

Abstract : Excessive maternal caffeine consumption can lead to fetal and neonatal pathology, but the underlying mechanisms have not been determined. Here, we report that low doses of caffeine generate seizures when applied in conjunction with brief anoxic episodes in the hippocampus of neonatal rats in vitro. In control conditions, brief (4-6 minutes) anoxic episodes reversibly depressed evoked synaptic responses and blocked the physiological pattern of network activity. In the presence of caffeine (50 microM), similar anoxic episodes generated ictal (29%) or interictal (33%) epileptiform activities often followed during reoxygenation by recurrent spontaneous seizure activity that persisted for several hours. These effects are likely mediated by a blockade of adenosine receptors by caffeine because (1) in control conditions, caffeine antagonized the inhibitory effect of selective A1 receptor agonist N6-cyclopentyladenosine on excitatory synaptic responses, and (2) epileptogenic effects of caffeine were reproduced by selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and theophylline. Our findings suggest that endogenous adenosine released during anoxia acting via A1 receptors prevents seizures in the neonatal hippocampus and that the antagonism of these receptors by caffeine leads to epileptogenesis. This study suggests concerns about the safety of caffeine in the fetus and newborn.
Document type :
Journal articles
Complete list of metadatas

Cited literature [70 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00486274
Contributor : Roman Tyzio <>
Submitted on : Tuesday, May 25, 2010 - 2:40:49 PM
Last modification on : Friday, March 27, 2020 - 2:23:45 AM
Long-term archiving on: : Thursday, December 1, 2016 - 12:58:00 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

  • HAL Id : inserm-00486274, version 1
  • PUBMED : 10401785

Collections

Citation

Volodymyr Dzhala, Luc Desfreres, Zare Melyan, Yehezkel Ben-Ari, Roustem Khazipov. Epileptogenic action of caffeine during anoxia in the neonatal rat hippocampus.. Annals of Neurology, Wiley, 1999, 46 (1), pp.95-102. ⟨inserm-00486274⟩

Share

Metrics

Record views

152