Abstract
The increase in osteopontin (OPN) levels after stroke induces neural protection by activating Akt signaling and inhibiting GS3Kβ, iNOS, and NF-κB. This study investigated the effect of a high-fat diet rich in corn oil (CO-HFD) on infarct size and memory function in rats after induction of cerebral ischemia in rats and investigated its effect on the expression of OPN/Akt/iNOS/NF-κB signaling pathways. Rats were initially fed a standard diet (STD, 3.82 kcal/g; 9.4%, from fat) or a CO-HFD (5.4 kcal/g, 40% from fat) for 12 weeks. Then, both groups were further subdivided into either sham group or group exposed to cerebral ischemia by the middle cerebral artery occlusion (MCAO) protocol. Compared with sham-operated rats fed STD diet, neurological scores and both short- and long-term memory functions were significantly impaired in sham-operated CO-HFD-fed rats. In addition, brains collected from CO-HFD-fed rats showed lower protein levels of OPN, p-Akt (Thr
), p-GS3Kβ (Ser
), and Bcl-2 and had higher protein levels of iNOS, cleaved caspase-3, nuclear NF-κB p65, and cytoplasmic cytochrome C. However, once exposed to MCAO surgery, similar but more profound alterations of all these biochemical parameters with more severe impairment in short- and long-term memory functions and larger infarct size were noticed in the brains of CO-HFD-fed rats as compared with STD-fed rats exposed to MCAO. In conclusion, chronic consumption of CO-HFD induces memory impairments and worsens memory function recovery and infarct size after cerebral ischemia in rats by reducing levels of OPN, inhibiting the activation of Akt and activating iNOS and NF-κB.