Neurochemical analysis of focal ischemia in rats.
OBJECTIVE
Increases in uric acid follow experimental stroke, which may be related to free radical formation by xanthine oxidase. The present study examined the time course of changes in xanthine and uric acid and their relationship to changes in the free radical scavengers glutathione, cysteine, and ascorbic acid.


METHODS
Focal ischemia was induced by occluding the middle cerebral artery, followed by transient occlusion of the common carotid arteries for 60 minutes. At varying time points, animals were sacrificed, and ischemic cortex was dissected. Neurochemical measurements were made by high-performance liquid chromatography with 16-sensor electrochemical detection.


RESULTS
Marked increases in uric acid were seen at all time points, with a maximal increase at 1 day and a persistent increase lasting up to 21 days. There were smaller reciprocal decreases in xanthine. Glutathione, cysteine, and ascorbic acid showed significant decreases, consistent with the generation of free radicals. Reductions in levels of cysteine and glutathione were significantly correlated with increases in uric acid levels.


CONCLUSIONS
These findings confirm marked alterations in purine metabolism following focal ischemia and suggest that xanthine oxidase contributes to the generation of free radicals.
Uemura
Y
Y
Stroke Research Laboratory, Massachusetts General Hospital, Boston 02114.
Miller
J M
JM
Matson
W R
WR
Beal
M F
MF
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006151:Guanosine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D015102:3,4-Dihydroxyphenylacetic Acid; D006151:Guanosine; D014527:Uric Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D014969:Xanthine Oxidase; D005978:Glutathione; D003545:Cysteine