Also from SFN, this study shows that when given several days prior to an ischemic insult, CX-614 ELIMINATED cell death from the ischemia. BDNF given directly also eliminated cell death -
>>> Program#/Poster#: 759.17/FF13
Title: Intermittent ampakine treatment sustains increased BDNF levels and provides neuroprotection from ischemia in vitro
Location: Georgia World Congress Center: Halls B3-B5
Presentation Start/End Time: Wednesday, Oct 18, 2006, 8:00 AM - 9:00 AM
Authors: *E. A. PINEDA, J. C. LAUTERBORN, C. M. GALL;
Anat & Neurobiol, Univ California-Irvine, Irvine, CA.
Previous studies have shown that positive modulators of AMPA-class glutamate receptors (ampakines) increase neuronal Brain Derived Neurotrophic factor (BDNF) gene expression and protein content. BDNF is known to reduce neuronal vulnerability to ischemic insult. The aim of the present study was to test if ampakine-induced increases in endogenous BDNF expression reduce neuronal cell death with ischemic insult of cultured hippocampal slices. We have shown that spaced ampakine treatments (50 µM CX614, 3hr/day) can sustain increased BDNF protein levels in hippocampal slices as assessed with ELISA and western blots. Using the in vitro hippocampal slice model of ischemic insult described by Frantseva et al. (1999) we find that 45 min submersion in deoxygenated, glucose free aCSF results in significant CA1 cell death as assessed by FluoroJade labeling and Lactate Dehydrogenase activity assays 24 hrs after ischemia. This cell death is eliminated by pretreatment with ampakine CX614 (3 hrs/day for 2 days; last treatment 21 hrs before insult) or exogenous BDNF application. The neuroprotective effect of ampakine pretreatment was blocked by the tyrosine kinase inhibitor k252a or the BDNF scavenger TrkB-Fc applied during ampakine pretreatment and post-ischemic intervals. These results indicate that ampakine-induced increases in endogenous BDNF mediate protection from ischemic insult, and support the possibility of using ampakines as therapeutics to enhance endogenous neurotrophin expression and promote neuronal survival after ischemia. <<<
