Bis(7)-tacrine, a promising anti-Alzheimer's dimer, affords dose- and time-dependent neuroprotection against transient focal cerebral ischemia

Yuming Zhao, Wenming Li, Peter C.Y. Chow, Dickson T.K. Lau, Nelson T.K. Lee, Yuanping Pang, Xuejun Zhang, Xiaoliang Wang, Yifan Han

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Bis(7)-tacrine, a promising anti-Alzheimer's dimer, has been shown to have multiple neuroprotective activities in vitro. Here, we investigate whether bis(7)-tacrine attenuates focal cerebral ischemic impairment in vivo. Cerebral ischemia was induced in Sprague-Dawley rats by transient (2 h) middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Bis(7)-tacrine administered intraperitoneally 15 min after ischemia dose-dependently improved neurological behavior deficits and reduced both cerebral infarct volume and edema. The TUNEL staining assay showed that bis(7)-tacrine attenuated neuronal apoptosis in the penumbral region. Compared with that for memantine, a moderately effective N-methyl-d-aspartate (NMDA) receptor antagonist with a similar affinity and potency to bis(7)-tacrine in blocking NMDA receptors, the therapeutic window for bis(7)-tacrine was wider and lasted up to 6 h after the onset of ischemia. Bis(7)-tacrine did not affect physiological parameters or regional cerebral blood flow during either the occlusion period or the early reperfusion stage. In conclusion, bis(7)-tacrine dose- and time-dependently protected against acute focal cerebral ischemic insults, possibly through the drug's anti-apoptotic effects during multiple events in the ischemic cascade.

Original languageEnglish (US)
Pages (from-to)160-164
Number of pages5
JournalNeuroscience Letters
Volume439
Issue number2
DOIs
StatePublished - Jul 11 2008

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Keywords

  • Bis(7)-tacrine
  • Cerebral ischemia
  • Memantine
  • Multiple targets
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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