Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Because of the fact that there is still no specific treatment for perinatal bra...Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology, the search of new neuroprotective therapies is of great interest. In this regard, therapeutic possibilities of the endocannabinoid system have grown lately. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. Concerning perinatal asphyxia, the neuroprotective role of this endogenous system is emerging these years. The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.展开更多
Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level...Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.展开更多
基金supported by grants from Fondo de Investigación Sanitaria of Spanish Ministry of Health(PS09/02326)the Basque Government(GCI-07/79,IT-287-07)
文摘Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology, the search of new neuroprotective therapies is of great interest. In this regard, therapeutic possibilities of the endocannabinoid system have grown lately. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. Concerning perinatal asphyxia, the neuroprotective role of this endogenous system is emerging these years. The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.
基金funded by Grants PID2021-127191OB-I00,RTI2018-101708-A-I00,PRE2018-084542 and PRE2022-102680 funded by MCIN/AEI/10.13039/501100011033 and by“ERDF A way of making Europe”Grant RYC2018-025502-I is funded by MCIN/AEI/10.13039/501100011033 and by“ESF Investing in your future”+1 种基金Grant MDM-20170720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agencysupported by Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATA-MP)。
文摘Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.
