Acute neurovascular unit protective action of pinocembrin against permanent cerebral ischemia in rats.
Acute vascular- and neuroprotective effects of pinocembrin (1) were evaluated in a rat model of focal cerebral ischemia. Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) for 24 h. 5,7-Dihydroxyflavanone (compound 1; at 3, 10, or 30 mg/kg), intravenously injected at 0, 8, and 16 h after MCAO, reduced the cerebral infarct volumes by 47, 39, and 37%, respectively, as visualized by 2,3,5-triphenyltetrazolium chloride staining (P < 0.01). Treatment with 1 also reduced brain swelling and improved behavioral deficits significantly (P < 0.01 and 0.05, respectively). To evaluate the effect of 1 on blood-brain barrier (BBB) disruption, mixture of Evans Blue (EB) and sodium fluorescein (NF) was intravenously injected immediately after MCAO. Global NF/EB uptake and fluorescence imaging of local BBB disruption were measured. Treatment with compound 1 reduced the leakage of both dyes, manifesting a preventive action in BBB integrity. This is the first time to demonstrate that 1 has acute neurovascular protective action against permanent focal cerebral ischemia. The mechanism of neurovascular protective action of 1 is under investigation.
Gao
Mei
M
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
Liu
Rui
R
Zhu
Shen-Yin
SY
Du
Guan-Hua
GH
D000818:Animals; D001929:Brain Edema / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005070:Evans Blue; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D019793:Fluorescein; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D044950:Flavanones; D018696:Neuroprotective Agents; D005070:Evans Blue; C016063:pinocembrin; D010100:Oxygen; D019793:Fluorescein