Inhibitory effects of chiral 3-n-butylphthalide on inflammation following focal ischemic brain injury in rats.
OBJECTIVE
To evaluate the degree of neutrophil infiltration into ischemic tissue after transient focal cerebral ischemia, and to examine the effects of chiral 3-n-butylphthalide (NBP) on this inflammatory process.


METHODS
After a 24-h reperfusion following transient cerebral ischemia, two different techniques, histologic analysis and modified myeloperoxidase (MPO)-quantification method, were utilized to identify the infiltration of neutrophils into cerebral tissue following ischemia. The expression of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha(TNF-alpha) in the ischemic zone were observed by immunohistochemistry, Western blot, and in situ hybridization techniques.


RESULTS
In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-alpha blue purple-positive neurons induced by ischemia-reperfusion injury.


CONCLUSIONS
The results indicate that the increase in neutrophils infiltration into the infarct site implicated postischemic brain injury, and NBP was effective in protecting the ischemic sites following ischemic insult.
Xu
H L
HL
Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
Feng
Y P
YP
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D001572:Benzofurans; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C027125:3-n-butylphthalide; D009195:Peroxidase