Liposomal curcumin nanocarrier ameliorates synaptic dysfunction after intracerebral hemorrhage

Background

Neuroinflammation and synaptic dysfunction in the medial prefrontal cortex (mPFC) contribute to cognitive impairment after intracerebral hemorrhage (ICH). Curcumin, a natural polyphenol from Curcuma longa, has anti-inflammatory properties but limited bioavailability.

Methods

Liposomal curcumin (Lipo-Cur, 103.2 nm, 74% encapsulation) was prepared by thin-film hydration. Adult male rats were assigned to Sham, ICH (collagenase + empty liposomes), and ICH-Cur (collagenase + Lipo-Cur, 30 mg/kg, i.p. at 2, 24, 48 h post-surgery). On day 7, we assessed NLRP3/caspase-1 inflammasome activation, BDNF/TrkB/CREB/Erk signaling, PSD-95 expression, neuronal survival (Nissl staining), and working memory (Y-maze).

Results

Lipo-Cur significantly suppressed NLRP3/caspase-1, restored p-CREB/CREB and p-TrkB/TrkB, normalized p-Erk/Erk, and upregulated PSD-95 (all p < 0.01). It also reduced neuronal loss, restored BDNF (p < 0.05), attenuated NLRP3 (p < 0.01), and improved Y-maze alternation (p < 0.001) without affecting locomotion.

Conclusion

These findings suggest that liposomal curcumin exerts neuroprotective effects in the mPFC after ICH, likely through mechanisms involving suppression of NLRP3/caspase-1 and enhancement of BDNF/TrkB/CREB signaling. This supports its potential as a natural product-based therapeutic for stroke-induced cognitive impairment, though further mechanistic studies are warranted.