Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study.
OBJECTIVE
It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31P and 1H magnetic resonance spectroscopy.


METHODS
Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.


RESULTS
In 31P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (-14% and -23%) and N-acetylaspartate:choline (-21% and -17%) ratios after 2 weeks and 8 months of diabetes, respectively.


CONCLUSIONS
No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic rats were shown by 1H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes.
Biessels
G J
GJ
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, The Netherlands.
Braun
K P
KP
de Graaf
R A
RA
van Eijsden
P
P
Gispen
W H
WH
Nicolay
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004734:Energy Metabolism; D006859:Hydrogen; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D007773:Lactates; D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D001224:Aspartic Acid; D006859:Hydrogen; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline