Effect of pterostilbene on cognitive function, and histone deacetylase and BDNF/CREB pathway following ischemia reperfusion injury in mice.

OBJECTIVE: To investigate the effect of pterostilbene (PTE), a natural dimethyl ether analog of resveratrol with higher bioavailability, on cognitive recovery after cerebral ischemia reperfusion (IR) injury and its potential mechanisms.

METHODS: Mice were subjected to middle cerebral artery occlusion and assigned to Sham, IR, PTE+IR, and PTE+Zinc Protoporphyrin (ZnPP)+IR groups. Cognitive function was assessed using the Morris water maze. Cerebral infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal apoptosis was determined via TUNEL assay. The protein levels of postsynaptic density protein 95 (PSD-95), phosphorylated cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and histone deacetylases (HDACs) in the hippocampus were measured by western blot.

RESULTS: PTE treatment significantly reduced cerebral infarct volume, alleviated cognitive deficits, and inhibited neuronal apoptosis in the hippocampus. At the molecular level, PTE up-regulated the expression of PSD-95, p-CREB, and BDNF, while down-regulating HDAC (1, 2, 3, 4, 7) levels. The beneficial effects of PTE were partially reversed by the HO-1 inhibitor ZnPP.

CONCLUSIONS: PTE ameliorates cognitive impairment induced by cerebral IR injury, potentially through activating the BDNF/CREB pathway and inhibiting HDAC expression. This suggests PTE as a promising neuroprotective agent for post-stroke cognitive recovery.