Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.
Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.
Department of in vivo NMR, Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands.
R M
RM
Dijkhuizen
M
M
van Lookeren Campagne
T
T
Niendorf
W
W
Dreher
A
A
van der Toorn
M
M
Hoehn-Berlage
H B
HB
Verheul
C A
CA
Tulleken
D
D
Leibfritz
K A
KA
Hossmann
K
K
Nicolay
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005471:Fluoroscopy; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D010758:Phosphorus; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate