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

• We detected the expression of RAGE in a rat model of SAH.
• The level of RAGE expression is significantly increased after SAH.
• Enhanced accumulation of RAGE was observed in neuron and microglia rather than astrocyte in the rat cortex after SAH.
• RAGE might be involved in the damaging inflammatory response after SAH.

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.