Effects of creatine and cyclocreatine supplementation on kainate induced injury in pre-pubescent rats.

PURPOSE: 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. CONCLUSION: Energy precursor supplementation in the doses used did not have neuroprotective effects in the kainate or kainate-phenobarbital models in pre-pubescent rats.

Duke Scholars

Author Mohamad Abdul Mikati Pediatrics, Neurology