Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 22, Issue 6, Pages 697-704Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00004647-200206000-00008
Keywords
rat brain; single-strand breaks; double-strand breaks; MK-801; DPQ; PARP
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The single-cell gel electrophoresis (comet assay) was used to evaluate the possibility of detecting single-strand breaks of brain DNA in the early phase of ischemia. Four hours after occlusion of the middle cerebral artery (MCAO) in rats, the percentage of DNA migrating into the comet tail (indicating the presence of breaks) increased from 11.4 +/- 4.70 to 34.7 +/- 9.2 (means +/-SD) in the cauclate and front 9.9 +/- 4.3 to 42.8 +/- 14.1 in the cortex. Interestingly, a subpopulation of cells exhibiting higher resistance to the ischemic insult was present in the caudate putamen, but not in the cortex. Administration of MK801, an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, (1 mg/kg subcutaneously, 10 minutes before MCAO), reduced the ischemia-induced DNA breaks and the infarct volume, suggesting that excessive Stimulation of NMDA receptors contributes to the formation of both DNA damage and infarct volume. In contrast. DPQ, an inhibitor of poly(ADP-ribose) polymerase (PARP) (10 mg/kg intraperitoneally, 2 hours before and 1 hour after MCAO), reduced the infarct volume but not DNA damage, suggesting that the neuroprotective actions of PARP inhibitors occur at a later step of the processes leading to postischemic neuronal death.
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