Effects of creatine and cyclocreatine supplementation on kainate induced injury in pre-pubescent rats.
OBJECTIVE
To investigate if energy precursor supplementation is neuroprotective in two neuroexcitotoxicity models; the kainate and the kainate followed by chronic phenobarbital models.


METHODS
Rats in experiment 1 received 1% creatine or cyclocreatine chow from age (P) 21-65 days, underwent kainate induced status epilepticus on P35 and were compared, as adults, to kainate alone rats and to normal controls. Rats in experiment 2 received 1% creatine chow (P21-P85), underwent kainate status epilepticus on P35, received daily phenobarbital (or saline) injections (P36-P85) and were compared, as adults, to kainate, kainate-phenobarbital and to normal control rats that received regular chow.


RESULTS
In experiment 1, the cyclocreatine-kainate group had increased emotionality and visuospatial learning deficits on the handling and watermaze tests as compared to all other groups. Creatine supplementation did not have any effects. In experiment 2, creatine supplementation did not prevent spontaneous recurrent seizures, aggressivity on the handling test or hippocampal histologic injury.


CONCLUSIONS
Energy precursor supplementation in the doses used did not have neuroprotective effects in the kainate or kainate-phenobarbital models in pre-pubescent rats.
Mikati
Mohamad A
MA
Adult and Pediatric Epilepsy Program, Department of Pediatrics, American University of Beirut, Beirut, Lebanon. mamikati@aub.edu.lb
Kurdit
Rana M
RM
Rahmeh
Amal A
AA
Farhat
Firas
F
Abu Rialy
Suha
S
Lteif
Lina
L
Francis
Elie
E
Geha
George
G
Maraashli
Wael
W
D000208:Acute Disease; D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants; D003401:Creatine / Q000008:administration & dosage*; D003404:Creatinine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D019587:Dietary Supplements; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid; D007859:Learning Disabilities / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010634:Phenobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012640:Seizures / Q000517:prevention & control; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D000927:Anticonvulsants; D018696:Neuroprotective Agents; C012260:cyclocreatine; D003404:Creatinine; D003401:Creatine; D007608:Kainic Acid; D010634:Phenobarbital