Inhibition of the Receptor for Advanced Glycation End-Products (RAGE) Attenuates Neuroinflammation While Sensitizing Cortical Neurons Towards Death in Experimental Subarachnoid Hemorrhage
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- 作者：Hua Li ; Jia-Sheng Yu ; Ding-Ding Zhang ; Yi-Qing Yang…
- 关键词：Subarachnoid hemorrhage ; Receptor for advanced glycation end products ; Inflammation ; Nuclear factor kappa B ; Apoptosis ; Autophagy
- 刊名：Molecular Neurobiology
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：54
- 期：1
- 页码：755-767
- 全文大小：
- 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
- 出版者：Springer US
- ISSN：1559-1182
- 卷排序：54
文摘
Subarachnoid hemorrhage (SAH) is a threatening and devastating neurological insult with high mortality and morbidity rates. Despite considerable efforts, the underlying pathophysiological mechanisms are still poorly understood. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been implicated in various pathological conditions. We previously showed that RAGE was upregulated and may be involved in pathophysiology of SAH. In the current study, we investigated its potential role in SAH. We found that the upregulation of RAGE after SAH was NF-κB-dependent positive feedback regulation. Further, pharmacological inhibition of RAGE attenuated neuroinflammation, indicating a possible contributive role of RAGE in inflammation-associated brain injury after SAH. Conversely, however, inhibition of RAGE sensitized neurons, exacerbating cell death, which correlated with augmented apoptosis and diminished autophagy, suggesting that activation of RAGE may protect against SAH-induced neuronal injury. Furthermore, we demonstrate that inhibition of RAGE significantly reduced brain edema and improved neurological function at day 1 but not at day 3 post-SAH. Taken together, these results suggest that RAGE exerts dual role after SAH. Our findings also suggest caution should be exercised in setting RAGE-targeted treatment for SAH.