Possible mechanisms underlying the protective effects of SY-21, an extract of a traditional Chinese herb, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampus.
We examined the neuroprotective actions of SY-21, a potent ingredient of a traditional Chinese herb, histologically. Transient brain ischemia (15 min) was induced by four-vessel occlusion in Sprague-Dawley rats. Administration of SY-21 20 min before or 6 h after brain ischemia significantly increased the number of surviving hippocampal CA1 pyramidal cells in rats subjected to transient brain ischemia followed by 5 days of reperfusion. Neuronal cell death resulting from ischemic events is associated with abnormal activation of the NMDA receptors. Tyrosine phosphorylation of the NMDA receptor subunit NR2A by Src or Fyn has been implicated in the up-regulation of NMDA receptor activity. In order to investigate the possible mechanism of the neuroprotective action of SY-21, we examined the effects of SY-21 on the ischemia/reperfusion-induced increases in tyrosine phosphorylation of the NMDA receptor subunit 2A (NR2A) and on the interactions involving NR2A, PSD-95 and Src/Fyn. We found that the increase in the tyrosine phosphorylation of NR2A induced by brain ischemia/reperfusion is suppressed by SY-21 administered 15 min before, or instantly after, brain ischemia. Also, SY-21 attenuated the increased interactions involving NR2A, PSD-95, Fyn and Src. These results demonstrate that SY-21 has a prominent neuroprotective action against brain ischemic insult, and the mechanism may involve the regulation of the tyrosine phosphorylation of NR2A by changing the above interactions.
Chen
Min
M
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
Wang
Yao
Y
Liu
Yong
Y
Hou
Xiao-Yu
XY
Zhang
Quan-Guang
QG
Meng
Fan-Jie
FJ
Zhang
Guang-Yi
GY
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D000076122:Disks Large Homolog 4 Protein; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020714:Maximum Tolerated Dose; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009842:Oligopeptides / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors
D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; C480825:SY 21; C040475:Src peptide; C033652:postsynaptic density proteins