Prolonged low-dose caffeine exposure protects against hippocampal damage but not against the occurrence of epilepsy in the lithium-pilocarpine model in the rat.
OBJECTIVE
Acute caffeine exposure has proconvulsant effects and worsens epileptic and ischemic neuronal damage. Surprisingly, prolonged caffeine exposure decreases the susceptibility to seizures and the extent of ischemic damage. We explored whether the exposure to a low long-term dose of caffeine could protect the brain from neuronal damage and epileptogenesis in the lithium-pilocarpine model of temporal lobe epilepsy.


METHODS
Rats received either plain tap water or water containing caffeine (0.3 g/L) for 15 days before the induction of status epilepticus (SE) by lithium-pilocarpine and for 7 days after SE. The extent of neuronal damage was assessed in the hippocampus and piriform and entorhinal cortices in brain sections stained with thionine and obtained from animals killed 7 days after SE. The latency to spontaneous recurrent seizures was controlled by video monitoring.


RESULTS
Caffeine treatment induced a marked, almost total neuroprotection in CA1 and a very limited protection in the hilus of the dentate gyrus, whereas damage in layers III-IV of the piriform cortex was slightly worsened by the treatment. All rats, whether they received caffeine or plain tap water, became epileptic after the same latency (17-19 days).


CONCLUSIONS
Thus these data extend the neuroprotective effects of low long-term caffeine exposure to epileptic damage and confirm that the sole protection of the Ammon's horn has no influence on the genesis of spontaneous recurrent seizures in this model.
Rigoulot
Marie-Aude
MA
INSERM U398, Université Louis Pasteur, Strasbourg, France.
Leroy
Claire
C
Koning
Estelle
E
Ferrandon
Arielle
A
Nehlig
Astrid
A
D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D018021:Lithium Chloride / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D000927:Anticonvulsants; D003292:Convulsants; D018696:Neuroprotective Agents; D010862:Pilocarpine; D002110:Caffeine; D018021:Lithium Chloride