fps-zm1 and ethyl-pyruvate

fps-zm1 has been researched along with ethyl-pyruvate* in 3 studies

Other Studies

3 other study(ies) available for fps-zm1 and ethyl-pyruvate

ArticleYear
HMGB1 promotes neurovascular remodeling via Rage in the late phase of subarachnoid hemorrhage.
    Brain research, 2017, Sep-01, Volume: 1670

    High-mobility group box1 (HMGB1) is a nuclear protein widely expressed in the central nervous system. Extracellular HMGB1 serves as a proinflammatory cytokine and contributes to brain injury during the acute stage post-stroke. Recently, increasing evidence has demonstrated beneficial effects of HMGB1 in some types of brain injury, but little is known about its effects during the late phase of subarachnoid hemorrhage (SAH). This study was designed to explore the potential roles and mechanisms of HMGB1 and its receptor, receptor for advanced glycation end-products (Rage), on brain recovery in the late stage of experimental SAH. Two inhibitors of HMGB1, ethyl pyruvate and glycyrrhizin (EP and GA), and Rage antagonist FPS-ZM1 were used to determine whether HMGB1 promotes brain recovery after SAH. The administration of EP, GA, and FPS-ZM1 effectively reduced HMGB1 and Rage expression. Correspondingly, protein levels of beneficial growth factors (NGF, BDNF, and VEGF) and numbers of BrdU and DCX positive neurons in the cortex were also decreased. The biphasic roles of HMGB1 may be based on the different redox modifications of cysteine residues. In this research, rats injected with two different redox status HMGB1 showed different prognosises at 7-14day after SAH. Recombinant HMGB1 can promote cytokine stimulating activity and aggravate brain injury. However, oxidized HMGB1 was unable to stimulate TNF production but can promote brain recovery by promoting neurotrophin expression. In conclusion, our investigation identified that HMGB1 promotes neurovascular recovery via Rage and may act in the oxidized state in the late stage of SAH.

    Topics: Animals; Benzamides; Brain; Brain Injuries; Cerebral Cortex; Disease Models, Animal; Doublecortin Protein; Glycyrrhizic Acid; HMGB1 Protein; Male; Neurons; Pyruvates; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Recombinant Proteins; Signal Transduction; Subarachnoid Hemorrhage; Vascular Remodeling

2017
HMGB1 may act via RAGE to promote angiogenesis in the later phase after intracerebral hemorrhage.
    Neuroscience, 2015, Jun-04, Volume: 295

    Following intracerebral hemorrhage (ICH), high-mobility group box 1 protein (HMGB1) may promote vascular remodeling. Whether HMGB1 supports angiogenesis after ICH is unclear, as are the receptors and downstream signaling pathway(s) involved. We used the rat model of collagenase-induced ICH to determine whether HMGB1 acts via the receptor for advanced glycation end-products (RAGE) to upregulate vascular endothelial growth factor (VEGF), a potent mitogen of endothelial cells and key regulator of normal and abnormal angiogenesis in the late phase of injury. At 3d after ICH induction, rats were treated with saline, ethyl pyruvate (EP) or N-benzyl-4-chloro-N-cyclohexylbenzamide (FPS-ZM1). ICH induced the movement of HMGB1 from the nucleus into the cytoplasm. Levels of HMGB1 and RAGE in the ipsilateral striatum increased within a few days of induction and continued to rise for 7-14d afterward. By 14d after induction, levels of VEGF and vessel density were higher than in the Sham group. Administering EP 3 days after ICH induction prevented much of the stroke-induced increases in vessel density and in expression of HMGB1, RAGE, and VEGF. Administering FPS-ZM1 after ICH blocked much of the stroke-induced increases in vessel density and VEGF expression. Our results suggest that after ICH, HMGB1 may upregulate VEGF in the ipsilateral striatum predominantly via RAGE. Hence, targeting the HMGB1/RAGE signaling pathway may help reduce inappropriate angiogenesis after ICH.

    Topics: Animals; Benzamides; Cerebral Hemorrhage; Collagenases; Corpus Striatum; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Functional Laterality; Gene Expression Regulation; Glial Fibrillary Acidic Protein; HMGB1 Protein; Male; Neovascularization, Physiologic; Pyruvates; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Up-Regulation; Vascular Endothelial Growth Factor A

2015
Blockade of high mobility group box-1 signaling via the receptor for advanced glycation end-products ameliorates inflammatory damage after acute intracerebral hemorrhage.
    Neuroscience letters, 2015, Nov-16, Volume: 609

    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.

    Topics: Acute Disease; Animals; Apoptosis; Benzamides; Brain; Brain Edema; Cerebral Hemorrhage; HMGB1 Protein; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 9; Pyruvates; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4

2015
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