Ischemic postconditioning (IPost) has been shown to attenuate cerebral 
ischemia-reperfusion injury. However, the mechanism remains elusive. Because 
opening of the mitochondrial permeability transition pore (MPTP) is a crucial 
determinant of cell death after ischemia-reperfusion, we hypothesized that the 
neuroprotective effect of IPost may be associated with inhibition of MPTP 
opening. In part 1 of this study, pentobarbital-anesthetized rats subjected to 
middle cerebral artery occlusion for 90 min, followed by reperfusion for 72 h, 
were assigned to receive one of the following treatments: three cycles of IPost 
(15s each), intracerebroventricular injection of saline (control), 
administration of the MPTP inhibitor cyclosporin A (CsA) (2 μmol/L, 15 μL) or 
its vehicle alcohol, administration of the MPTP opener atractyloside (Atr) (2 
mmol/L, 15 μL), or IPost plus CsA/Atr treatment. Neurological deficit scores 
(NDS) and infarct volumes were assessed. Mitochondrial ultrastructure and 
swelling were also examined after reperfusion. In part 2, control and IPost 
groups underwent ischemia (90 min) and reperfusion (15 min). CsA and Atr groups 
were treated as described in part 1. Brain mitochondria were isolated after 
reperfusion and MPTP activity was evaluated. IPost or CsA treatment 
significantly improved NDS and reduced infarction volume, while Atr reversed the 
neuroprotective effects of IPost, and attenuated the decrease in mitochondrial 
swelling induced by IPost or CsA. Thus, inhibiting MPTP opening may play a 
crucial role in the neuroprotective effects of IPost, which may have potential 
clinical value against cerebral ischemia-reperfusion injury.