Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6280316 | Neuroscience Letters | 2015 | 30 Pages |
Abstract
Intracerebral hemorrhage (ICH) is a devastating disease with no specific treatment. Increasing evidence indicates that inflammatory response plays a critical role in ICH-induced damage. High mobility group box-1 protein (HMGB1) may trigger inflammatory response via three putative receptors: receptor for advanced glycation end-products (RAGE), toll-like receptor-2 (TLR2) and toll-like receptor-4 (TLR4). Which receptor participates in HMGB1-induced inflammation during acute ICH is unknown. Using a rat model to examine the early phase of injury in collagenase-induced ICH, we found that treating animals with HMGB1 antagonist significantly reduced the expression of all three receptors. Treating animals with the HMGB1 antagonist EP or RAGE antagonist FPS-ZM1 significantly reduced inflammatory cell infiltration and expression of IL-1β, matrix metalloproteinase-9 in the perihematoma after ICH. Treatment with EP or FPS-ZM1 also led to greater neurobehavioral function and less brain edema, hemorrhage volume and brain damage after ICH. In contrast, treatment with TLR2/4 antagonists did not significantly affect these post-ICH outcomes. Our results suggest that RAGE may play a specific role in the acute phase of ICH, so targeting the HMGB1-RAGE signaling pathway may be a promising therapeutic strategy.
Keywords
NSEIL-1βDAPIMMP-9TLR2GFAPmNSSPVDFIBA1HMGB1IL-6TLR4RAGETAK-2424′,6-diamidino-2-phenylindoleNeuron-specific enolaseH&EEthyl pyruvateinflammationsodium dodecyl sulfate-polyacrylamide gel electrophoresisSDS-PAGEinterleukin-6Interleukin-1βtumor necrosis factor-αTUNELintracerebral hemorrhageTNF-αMatrix metalloproteinase-9ICHmodified neurological severity scoreHematoxylin and EosinGlial fibrillary acidic proteinPolyvinylidene fluoridehigh mobility group box-1Receptor for advanced glycation end-products
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Authors
Dan Li, Chunyan Lei, Shuting Zhang, Shihong Zhang, Ming Liu, Bo Wu,