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.