Temporal changes in proton MRS metabolites after kainic acid-induced seizures in rat brain.
OBJECTIVE
In situ 1H-magnetic resonance spectroscopy (MRS) was used to study temporal metabolic changes in a rat model of temporal lobe epilepsy (TLE) by using kainic acid (KA).


METHODS
Rat brains were scanned at the level of the hippocampal body for MRS measurements. Relative ratios of N-acetyl groups (NA: N-acetylaspartate and N-acetylaspartyl glutamate), choline, and lactate (Lac) over creatine (Cr) were calculated.


RESULTS
NA/Cr ratios increased significantly during the ictal phase. During the postictal and interictal phases, the NA/Cr ratio decreased. There was a significant and prolonged increase of the lactate/Cr ratio in the hippocampi of rats that started 1 h after the onset of KA-induced seizure activity and persisted up to 24 h after the injection. The prolonged lactate/Cr increase in an area susceptible to neuronal damage (e.g., hippocampus) correlated with the onset of seizure activity but remained elevated thereafter.


CONCLUSIONS
The ictal and early postictal increase in lactate ratios may reflect increased cellular activity and metabolism resulting from KA excitotoxicity. Assuming that the changes in NA/Cr ratios are due to NAA increase, we speculate that an activation of the N-acetylaspartylglutamate (NAAG) dipeptidase pathway may explain the ictal increase in NA/Cr ratios. The late postictal decrease in NA/Cr ratios is a reflection of KA-induced neuronal cell loss.
Najm
I M
IM
Department of Neurology, Cleveland Clinic Foundation, Ohio 44195, USA.
Wang
Y
Y
Hong
S C
SC
Lüders
H O
HO
Ng
T C
TC
Comair
Y G
YG
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002794:Choline / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism
D004151:Dipeptides; D009479:Neuropeptides; D011522:Protons; C027172:isospaglumic acid; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003404:Creatinine; D002794:Choline; D007608:Kainic Acid