Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.
OBJECTIVE
Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia.


METHODS
We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion.


RESULTS
In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned to near-normal level by 168 hours after reperfusion. Brain MPO activity after transient MCA occlusion correlated well with the appearance of neutrophils. Depletion of neutrophils by RP3 treatment completely inhibited the increase in MPO activity in the ischemic brain after 24 hours of reperfusion. In addition, treatment with RP3 significantly attenuated the postischemic increase in brain water content at 24 hours after reperfusion. RP3 also significantly reduced the size of infarct area.


CONCLUSIONS
These results indicate that the increase in brain MPO activity after transient focal ischemia virtually reflects the neutrophil infiltration and that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.
Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co, LTD, Osaka, Japan.
Y
Y
Matsuo
H
H
Onodera
Y
Y
Shiga
M
M
Nakamura
M
M
Ninomiya
T
T
Kihara
K
K
Kogure
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology* / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology
D009195:Peroxidase