RT Journal Article SR Electronic T1 Ampakines Attenuate Staurosporine-induced Cell Death in Primary Cortical Neurons: Implications in the ‘Chemo-Brain’ Phenomenon JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3461 OP 3465 DO 10.21873/anticanres.12615 VO 38 IS 6 A1 DANIEL P. RADIN A1 GARY A. ROGERS A1 KIMBERLEY E. HEWITT A1 RICHARD PURCELL A1 ARNOLD LIPPA YR 2018 UL http://ar.iiarjournals.org/content/38/6/3461.abstract AB Background/Aim: Mounting evidence suggests that trophic cell signaling can be mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation. It has been demonstrated that exogenous application of brain-derived neurotrophic factor (BDNF) is highly neuroprotective in vitro against neurotoxic insults such as standard chemotherapies. Materials and Methods: Because positive allosteric modulation of AMPARs with ampakines can increase both BDNF mRNA and protein in vitro and in vivo, we examined whether application of the ampakines CX614 and CX729 promoted neuroprotection against staurosporine-induced cell death in rat primary cortical neurons using propidium iodide to stain for dead cells. Results: A transient 2-h pretreatment with CX614 or CX729 performed 24 h prior to staurosporine produced significant, time-dependent neuroprotection that was resistant to the AMPAR antagonists NBQX or GYKI 52466, suggesting that this effect may be independent of ion flow. Furthermore, the pretreatment time requirements of CX729 matched the time course for increased BDNF expression previously reported to occur in hippocampal slices, suggesting that increased neurotrophin expression might be associated with the neuroprotective effects conferred by ampakines. Conclusion: Our data demonstrate that ampakines may be able to perturb neuronal toxicity and peripheral neuropathy of front-line chemotherapies.