Expression and cell distribution of receptor for advanced glycation end-products in the rat cortex following experimental subarachnoid hemorrhage

Brain Res. 2014 Jan 16:1543:315-23. doi: 10.1016/j.brainres.2013.11.023. Epub 2013 Nov 26.

Abstract

Convincing evidence indicates that inflammation contributes to the adverse prognosis of subarachnoid hemorrhage (SAH). Some pro-inflammatory molecules such as high mobility group protein 1, S100 family of proteins, β-amyloid peptide, and macrophage antigen complex 1 have been involved in the damaging inflammation process following SAH. The receptor for advanced glycation end-products (RAGE) is a transmembrane receptor that senses these molecules and plays central role in inflammatory processes. This study aimed to determine the expression and cell distribution of RAGE in the brain cortex after SAH. Male Sprague-Dawley rats were randomly divided into sham group and SAH groups at 6 h, 12 h and on day 1, day 2 and day 3 (n=6 for each subgroup). SAH groups suffered experimental SAH by injection of 0.3 ml autologous blood into the prechiasmatic cistern. RAGE expression was measured by Western blot, real-time PCR, immunohistochemistry and immunofluorescence. Nuclear expression of p65 protein, the major subunit of nuclear factor kappa B, was also detected. Our data demonstrated that the expression levels of RAGE and nuclear p65 protein were both markedly increased after SAH. Moreover, there was a significant positive correlation between the expression of RAGE and that of p65 protein. Double immunofluorescence staining showed that RAGE was expressed by neuron and microglia rather than astrocyte after SAH. These results suggest that RAGE may be directly involved in the inflammatory response after SAH, and there might be important implications for further studies using specific RAGE antagonists to decrease inflammation-mediated brain injury following SAH.

Keywords: Aβ; CNS; GFAP; HMGB1; Iba1; Inflammation; Mac-1; NF-κB; NeuN; Nuclear factor kappa B; PCR; RAGE; Receptor for advanced glycation end-product; SAH; Subarachnoid hemorrhage; central nervous system; glialfibrillary acidic protein; high mobility group protein 1; ionized calcium binding adaptor molecule 1; macrophage antigen complex 1; neuron specific nuclear protein; nuclear factor kappa B; polymerase chain reaction; receptor for advanced glycation end-products; subarachnoid hemorrhage; β-amyloid peptide.

MeSH terms

  • Analysis of Variance
  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / metabolism*
  • Histones / metabolism
  • Male
  • NF-kappa B / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Subarachnoid Hemorrhage / pathology*
  • Time Factors

Substances

  • Glial Fibrillary Acidic Protein
  • Glycation End Products, Advanced
  • Histones
  • NF-kappa B
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Phosphopyruvate Hydratase