Greater resistance and lower contribution of free radicals to hypoxic neurotoxicity in immature rat brain compared to adult brain as revealed by dynamic changes in glucose metabolism.
Seven-day-old rat brain slices were incubated at 36C in oxygenated Krebs-Ringer solution containing [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG), and serial two-dimensional time-resolved images of [(18)F]FDG uptake by the slices were obtained. The Gjedde-Patlak graphical method was applied to the image data, and the duration limit of hypoxia loading that allowed recovery of the fractional rate constant (k3*) of [(18)F]FDG (proportional to the cerebral glucose metabolic rate) after hypoxia loading to the unloaded control level was 50 min, and MK-801 as an N-methyl-D-aspartate antagonist had neuroprotective effects, but PBN as a free radical scavenger was ineffective. In our previous study in adult (7-week-old) rat brains [Murata et al., Exp Neurol 2000, 164:269-279], the limit of the hypoxia loading time was 20 min, and both MK-801 and PBN were effective. In the immature rat brains, the ratio of aerobic glucose metabolism to the total glucose metabolism was low compared with the adult rat brains, suggesting only a slight involvement of free radicals in hypoxic neurotoxicity. These data suggest that the higher resistance of immature brains to hypoxia compared to that of adult brains is attributable to a lower involvement of free radicals due to a lower aerobic glucose metabolic rate.
Maruoka
N
N
Department of Neuropsychiatry, Biomedical Imaging Research Center, Fukui Medical University, Yoshida-gun, Fukui, Japan.
Murata
T
T
Omata
N
N
Fujibayashi
Y
Y
Waki
A
A
Yoshimoto
M
M
Yano
R
R
Yonekura
Y
Y
Wada
Y
Y
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development* / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging*; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D009924:Organ Culture Techniques; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D005609:Free Radicals; D009498:Neurotoxins; D005947:Glucose