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 language | English |
---|---|
Pages (from-to) | 160-164 |
Number of pages | 5 |
Journal | Neuroscience Letters |
Volume | 439 |
Issue number | 2 |
DOIs | |
Publication status | Published - 11 Jul 2008 |
Keywords
- Bis(7)-tacrine
- Cerebral ischemia
- Memantine
- Multiple targets
- Stroke
ASJC Scopus subject areas
- General Neuroscience