Homogeneous repair of nuclear genes after experimental stroke.
The repair of oxidative DNA lesions (ODLs) in the nucleus of ischemic cortical brain cells was examined following experimentally induced stroke by occluding the right middle cerebral artery and both common carotid arteries for 60-90 min followed by reperfusion in male long-Evans hooded rats. The control group consisted of sham-operated animals undergoing the same surgery without vessel occlusion. Using a gene-specific assay based upon the presence of Escherichia coli Fpg protein-sensitive sites, we noted that animals with stroke exhibited six and four ODLs per gene in the actin and DNA polymerase-beta genes, respectively. This was increased from one per four copies of each gene in the sham-operated control (p < 0.01). One half of the initial ODLs was repaired within 30 min, and 83% of them were repaired as early as 45 min of reperfusion. There was no further increase when gene repair was measured again at 2 h of reperfusion. The rates of active repair within 45 min of reperfusion were the same in these two genes (p = 0.103, ANOVA). BrdU (10 mg/kg) was administered via intraperitoneal injection at least one day before surgery. We observed that there was no significant incorporation of BrdU triphosphates into genomic DNA during active repair, but there were significant amounts of BrdU triphosphate in nuclear DNA after active repair. The result indicates that genomic repair of ODLs in the brain did not significantly incorporate BrdU, and the initiation of neurogenesis probably starts after the completion of repair in the brain.
Moore
N
N
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Okocha
F
F
Cui
J K
JK
Liu
Philip K
PK
D000818:Animals; D001921:Brain / Q000503:physiopathology* / Q000601:surgery; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000235:genetics*; D013537:Sutures
D004247:DNA; D001973:Bromodeoxyuridine