Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.
Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.
Johshita
H
H
Department of Neurosurgery, Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
Asano
T
T
Hanamura
T
T
Takakura
K
K
D000818:Animals; D001929:Brain Edema / Q000139:chemically induced / Q000209:etiology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002415:Cats; D002536:Cerebral Arteries; D002540:Cerebral Cortex; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003250:Constriction; D005260:Female; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D011427:Propiophenones / Q000009:adverse effects / Q000494:pharmacology*; D015424:Reperfusion; D013046:Specific Gravity
D011427:Propiophenones; C037467:2-aminomethyl-4-tert-butyl-6-propionylphenol; D007213:Indomethacin