Ghrelin is known to promote neuronal defense and survival against ischemic 
injury by inhibiting apoptotic processes. In the present study, we investigated 
the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the 
expression of which is increased after ischemic injury, in ghrelin-mediated 
neuroprotection during middle cerebral artery occlusion (MCAO). Both ghrelin and 
des-acyl ghrelin protected cortical neurons from ischemic injury. Ghrelin 
receptor specific antagonist abolished the protective effects of ghrelin, 
whereas those of des-acyl ghrelin were preserved, suggesting the involvement of 
a receptor that is distinct from GHS-R1a. The expression of Par-4 was increased 
by MCAO, which was attenuated by ghrelin and des-acyl ghrelin treatments. Both 
ghrelin and des-acyl ghrelin increased the Bcl-2/Bax ratio, prevented cytochrome 
c release, and inhibited caspase-3 activation. Our data indicate that des-acyl 
ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury 
through the inhibition of Par-4 expression and apoptotic molecules in 
mitochondrial pathway.