Curcumin, encapsulated in nano-sized PLGA, down-regulates nuclear factor κB (p65) and subarachnoid hemorrhage induced early brain injury in a rat model

Background: More and more evidence revealed early brain injury (EBI) may determine the final outcome in aneutismal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of nano-particle curcumin (nanocurcumin), a diarylheptanoid, on a SAH-induced EBI model. Methods: A rodent double hemorrhage model was employed. Nanocurcumin (75/150/300 mu g/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1 beta, IL-6, IL-8 and TNF-alpha (rt-PCR). Cerebral cortex was harvested for NF-kappa B (p50/p65) (western blot), caspases (rt-PCR) measurement. Results: Nanocurcumin significantly reduced the bio-expression of NF-kappa B (p65), when compared with the SAH groups. The levels of IL-1 beta and IL-6 were increased in animals subjected to SAH, compared with the healthy controls, but absent in the high dose nanocurcumin+SAH group. Moreover, the levels of TNF-alpha in the SAH groups were significantly elevated. Treatment with nanocurcumin (300 mu g/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300 mu g/kg nanocurcumin treatment groups (P < 0.05). Conclusion: Treatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-kappa B (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-alpha and IL-1 beta, which may contribute to the extrinsic antiapoptotic effect This study shows promise to support curcuminin, in a nanoparticle, could attenuate SAH induced EBI. (C) 2015 Elsevier B.V. All rights reserved.