Positive allosteric modulators of AMPA receptors are neuroprotective against lesions induced by an NMDA agonist in neonatal mouse brain

Four positive modulators of AMPA-type glutamate receptors (cyclothiazide, CX614, LY404187 and S18986-1) given in acute or chronic manner exerted a neuroprotective effect in lesions induced in postnatal day 5 (P5) mice by intracerebral injection of ibotenate, an NMDA agonist. The neuroprotective effects were mediated via the MAPK pathway since coinjection of the MEK Inhibitor, PD98059, blocked the neuroprotective effects. Administration of CX614 to neonatal mice was followed by upregulation of hippocampal and cortical BDNF expression.