Creatine Effects in Epileptic Rat Hippocampus Revealed by In Vivo Localized Proton Magnetic Resonance Spectroscopy.
Abstract number :
2.089
Submission category :
Year :
2001
Submission ID :
236
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
S. Vielhaber, MD, Neurology, University of Magdeburg Medical Center, Magdeburg, Germany; D. Stiller, PhD, Neurobiology, Leibniz Institute, Magdeburg, Germany; A. Kudin, PhD, Epileptology, University of Bonn Medical Center, Bonn, Germany; W.S. Kunz, PhD, E
RATIONALE: Possible neuroprotective opportunities attenuating the selective neuronal cell loss in hippocampal sclerosis are not well established yet. As the cascade of events leading to cell death involves impairment of mitochondria, a putative neuroprotective approach is the buffering of cellular energy levels by creatine administration. N-acetyl aspartate (NAA) detected by in vivo 1H-MR-spectroscopy has been proposed to be a marker for the neurodegenerative process. In this study we used the pilocarpine model of hippocampal sclerosis to determine by in vivo 1H-MRS and histology whether creatine administration is able to attenuate the epilepsy-induced decrease in hippocampal NAA levels and neuronal cell loss.
METHODS: Male Whistar-rats were fed with a diet containing 2% creatine (n = 4) or normal rat chow (n = 12) after the induction of status epilepticus by pilocarpine injection. Non-pilocarpine treated rats (n = 11) served as controls. After development of spontaneous seizures (25 days after pilocarpine injection), single voxel 1H-MRS of the hippocampus was performed and afterwards the animals were decapitated for hippcocampal histological work up.
RESULTS: In vivo 1H-MRS of the hippocampus revealed that the creatine diet led to an about 20 % increase of total creatine (p[lt]0.01). In response to the creatine administration we also observed significantly increased hippocampal NAA levels (p[lt]0.02). Surprisingly, histology demonstrated a significant higher neuronal cell loss in the epileptic hippocampus of the creatine-treated animals (p[lt]0.01).
CONCLUSIONS: Our findings confirm that NAA reduction in the epileptic hippocampus is associated with selective neuronal cell loss. In addition we could show in this animal model, that a recovery of NAA levels after creatine administration occurs in the epileptic hippocampus independently of the occurring neuronal cell loss. This indicates, that most possibly a compromised neuronal metabolism contributes to the observed reduction of NAA levels. In respect to putative neuroprotective implications of these findings, further studies are needed.