Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/15860
Title: Bis(7)-tacrine, a promising anti-Alzheimer's dimer, affords dose- and time-dependent neuroprotection against transient focal cerebral ischemia
Authors: Zhao, Y
Li, W
Chow, PCY
Lau, DTK
Lee, NTK
Pang, Y
Zhang, X
Wang, X
Han, Y 
Keywords: Bis(7)-tacrine
Cerebral ischemia
Memantine
Multiple targets
Stroke
Issue Date: 2008
Publisher: Elsevier
Source: Neuroscience letters, 2008, v. 439, no. 2, p. 160-164 How to cite?
Journal: Neuroscience letters 
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.
URI: http://hdl.handle.net/10397/15860
ISSN: 0304-3940
EISSN: 1872-7972
DOI: 10.1016/j.neulet.2008.05.007
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