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

Brain Res. 2015 May 22:1608:215-24. doi: 10.1016/j.brainres.2015.02.039. Epub 2015 Mar 5.

Abstract

Background: More and more evidence revealed early brain injury (EBI) may determine the final outcome in aneurismal 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 (75/150/300μg/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1β, IL-6, IL-8 and TNF-α (rt-PCR). Cerebral cortex was harvested for NF-κB (p50/p65) (western blot), caspases (rt-PCR) measurement.

Results: Nanocurcumin significantly reduced the bio-expression of NF-κB (p65), when compared with the SAH groups. The levels of IL-1β 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-α in the SAH groups were significantly elevated. Treatment with nanocurcumin (300μg/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300μg/kg nanocurcumin treatment groups (P<0.05).

Conclusion: Treatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-κB (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-α and IL-1β, which may contribute to the extrinsic antiapoptotic effect. This study shows promise to support curcuminin, in a nano-particle, could attenuate SAH induced EBI.

Keywords: Early brain injury; Nanocurcumin; Nuclear factor kappa-light-chain-enhancer of activated B cells; Subarachnoid hemorrhage; Tumor necrotic factor-α.

MeSH terms

  • Analysis of Variance
  • Animals
  • Biocompatible Materials / therapeutic use
  • Brain Injuries / complications*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Curcumin / therapeutic use*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects*
  • Enzyme Inhibitors / therapeutic use*
  • Lactic Acid / therapeutic use
  • Male
  • Neurologic Examination
  • Polyglycolic Acid / therapeutic use
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage* / drug therapy
  • Subarachnoid Hemorrhage* / etiology
  • Subarachnoid Hemorrhage* / pathology
  • Transcription Factor RelA / metabolism*

Substances

  • Biocompatible Materials
  • Cytokines
  • Enzyme Inhibitors
  • RNA, Messenger
  • Rela protein, rat
  • Transcription Factor RelA
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Caspase 3
  • Caspase 9
  • Curcumin