Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
High-quality Bi2-xPbxSr2 CaCu2O8+δ(Bi2212) single crystals have been successfully grown by the traveling solvent floating zone technique with a wide range of Pb substitution(x = 0–0.8).The samples are characterized ...High-quality Bi2-xPbxSr2 CaCu2O8+δ(Bi2212) single crystals have been successfully grown by the traveling solvent floating zone technique with a wide range of Pb substitution(x = 0–0.8).The samples are characterized by transmission electron microscope(TEM) and measured by high resolution laser-based angle-resolved photoemission spectroscopy(ARPES) with different photon energies.A systematic evolution of the electronic structure and superstructure with Pb substitution has been revealed for the first time.The superstructure shows a significant change with Pb substitution and the incommensurate modulation vector(Q) decreases with increasing Pb substitution.In the meantime, the superstructure intensity from ARPES measurements also decreases dramatically with increasing Pb concentration.The superstructure in Bi2212 can be effectively suppressed by Pb substitution and it nearly disappears with a Pb substitution of x = 0.8.We also find that the superstructure bands in ARPES measurements depend sensitively on the photon energy of lasers used;they can become even stronger than the main band when using a laser photon energy of 10.897 eV.These results provide important information on the origin of the incommensurate superstructure and its control and suppression in bismuth-based high temperature superconductors.展开更多
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2016YFA0300300 and 2017YFA0302900)the Strategic Priority Research Program(B)of the Chinese Academy of Sciences(Grant Nos.XDB07020300 and XDB25000000)+1 种基金the National Natural Science Foundation of China(Grant Nos.11334010 and 11534007)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2017013)
文摘High-quality Bi2-xPbxSr2 CaCu2O8+δ(Bi2212) single crystals have been successfully grown by the traveling solvent floating zone technique with a wide range of Pb substitution(x = 0–0.8).The samples are characterized by transmission electron microscope(TEM) and measured by high resolution laser-based angle-resolved photoemission spectroscopy(ARPES) with different photon energies.A systematic evolution of the electronic structure and superstructure with Pb substitution has been revealed for the first time.The superstructure shows a significant change with Pb substitution and the incommensurate modulation vector(Q) decreases with increasing Pb substitution.In the meantime, the superstructure intensity from ARPES measurements also decreases dramatically with increasing Pb concentration.The superstructure in Bi2212 can be effectively suppressed by Pb substitution and it nearly disappears with a Pb substitution of x = 0.8.We also find that the superstructure bands in ARPES measurements depend sensitively on the photon energy of lasers used;they can become even stronger than the main band when using a laser photon energy of 10.897 eV.These results provide important information on the origin of the incommensurate superstructure and its control and suppression in bismuth-based high temperature superconductors.
