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

Min Chen, Yao Wang, Yong Liu, Xiao Yu Hou, Quanguang Zhang, Fan Jie Meng, Guang Yi Zhang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalBrain Research
Volume989
Issue number2
DOIs
StatePublished - Nov 7 2003
Externally publishedYes

Fingerprint

Brain Ischemia
Reperfusion
Hippocampus
Tyrosine
N-Methyl-D-Aspartate Receptors
Phosphorylation
Pyramidal Cells
SY 21
Sprague Dawley Rats
N-methyl D-aspartate receptor subtype 2A
Cell Death
Up-Regulation
Ischemia
Brain

Keywords

  • Brain ischemia
  • Hippocampus
  • NMDA receptor
  • Neuroprotective action
  • Rat
  • SY-21

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

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. / Chen, Min; Wang, Yao; Liu, Yong; Hou, Xiao Yu; Zhang, Quanguang; Meng, Fan Jie; Zhang, Guang Yi.

In: Brain Research, Vol. 989, No. 2, 07.11.2003, p. 180-186.

Research output: Contribution to journalArticle

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abstract = "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.",
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AB - 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.

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