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, Yuan-Ping Pang, Xuejun Zhang, Xiaoliang Wang, Yifan Han

Research output: Contribution to journalArticle

21 Citations (Scopus)

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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Transient Ischemic Attack
Reperfusion
Cerebrovascular Circulation
Ischemia
Memantine
1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
Neuroprotection
Middle Cerebral Artery Infarction
Regional Blood Flow
In Situ Nick-End Labeling
Brain Ischemia
Sprague Dawley Rats
Edema
Apoptosis
Staining and Labeling
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bis(7)-tacrine, a promising anti-Alzheimer's dimer, affords dose- and time-dependent neuroprotection against transient focal cerebral ischemia. / Zhao, Yuming; Li, Wenming; Chow, Peter C Y; Lau, Dickson T K; Lee, Nelson T K; Pang, Yuan-Ping; Zhang, Xuejun; Wang, Xiaoliang; Han, Yifan.

In: Neuroscience Letters, Vol. 439, No. 2, 11.07.2008, p. 160-164.

Research output: Contribution to journalArticle

Zhao, Yuming ; Li, Wenming ; Chow, Peter C Y ; Lau, Dickson T K ; Lee, Nelson T K ; Pang, Yuan-Ping ; Zhang, Xuejun ; Wang, Xiaoliang ; Han, Yifan. / Bis(7)-tacrine, a promising anti-Alzheimer's dimer, affords dose- and time-dependent neuroprotection against transient focal cerebral ischemia. In: Neuroscience Letters. 2008 ; Vol. 439, No. 2. pp. 160-164.
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