Previous studies have demonstrated that plasma
resistin levels were increased in patients with
acute ischemic stroke. However, the role of
resistin after ischemic
brain injury is still unclear. In this study, we investigated the protective effects of
resistin on
cerebral ischemia/
reperfusion injury in a
middle cerebral artery occlusion mouse model. We found that
resistin (i.c.v.) significantly reduced
infarct volume and improved neurological deficits after 45 min of
ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of
resistin (10 µg/kg
body weight) also had protective effects on
infarct volume, indicating the crossing of
resistin through the impaired BBB after
ischemia injury.
Resistin treatment reduced cleaved
protein level of Poly(ADP-ribose)polymerase-1 (PARP-1), a marker of cellular apoptosis, showing the anti-apoptotic activity of
resistin.
Resistin increased the level of phosphorylated Akt after ischemic
brain injury. The
neuroprotective effect of
resistin was partially reversed by a PI3K inhibitor
wortmannin, demonstrating that the PI3K/Akt signal pathway is involved in the anti-apoptotic mechanisms of
resistin. Finally, we found that
resistin treatment improved neurological function recovery at 14 days
after treatment, including balance ability and muscle strength. Given these findings,
resistin may have therapeutic potential for the treatment of
stroke.