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The immune response after hypoxia-ischemia in a mouse model of preterm brain injury
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نویسنده
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albertsson a.-m. ,bi d. ,duan l. ,zhang x. ,leavenworth j.w. ,qiao l. ,zhu c. ,cardell s. ,cantor h. ,hagberg h. ,mallard c. ,wang x.
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منبع
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journal of neuroinflammation - 2014 - دوره : 11 - شماره : 0
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چکیده
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Background: preterm brain injury consists primarily of periventricular leukomalacia accompanied by elements of gray-matter injury,and these injuries are associated with cerebral palsy and cognitive impairments. inflammation is believed to be an important contributing factor to these injuries. the aim of this study was to examine the immune response in a postnatal day (pnd) 5 mouse model of preterm brain injury induced by hypoxia-ischemia (hi) that is characterized by focal white and gray-matter injury. methods: c57bl/6 mice at pnd 5 were subjected to unilateral hi induced by left carotid artery ligation and subsequent exposure to 10% o2 for 50 minutes,70 minutes,or 80 minutes. at seven days post-hi,the white/gray-matter injury was examined. the immune responses in the brain after hi were examined at different time points after hi using rt-pcr and immunohistochemical staining. results: hi for 70 minutes in pnd 5 mice induced local white-matter injury with focal cortical injury and hippocampal atrophy,features that are similar to those seen in preterm brain injury in human infants. hi for 50 minutes resulted in a small percentage of animals being injured,and hi for 80 minutes produced extensive infarction in multiple brain areas. various immune responses,including changes in transcription factors and cytokines that are associated with a t-helper (th)1/th17-type response,an increased number of cd4+ t-cells,and elevated levels of triggering receptor expressed on myeloid cells 2 (trem-2) and its adaptor protein dnax activation protein of 12 kda (dap12) were observed using the hi 70 minute preterm brain injury model. conclusions: we have established a reproducible model of hi in pnd 5 mice that produces consistent local white/gray-matter brain damage that is relevant to preterm brain injury in human infants. this model provides a useful tool for studying preterm brain injury. both innate and adaptive immune responses are observed after hi,and these show a strong pro-inflammatory th1/th17-type bias. such findings provide a critical foundation for future studies on the mechanism of preterm brain injury and suggest that blocking the th1/th17-type immune response might provide neuroprotection after preterm brain injury. © 2014 albertsson et al.; licensee biomed central ltd.
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کلیدواژه
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Brain injury; Hypoxia-ischemia; Immune response; Preterm
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آدرس
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perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30, Sweden, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of pediatrics,the third affiliated hospital of zhengzhou university,zhengzhou, China, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of pediatrics,the third affiliated hospital of zhengzhou university,zhengzhou, China, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of pediatrics,the third affiliated hospital of zhengzhou university,zhengzhou, China, department of cancer immunology and aids,dana-farber cancer institute,harvard medical school,boston,ma,united states,department of microbiology and immunobiology,division of immunology,harvard medical school,boston,ma, United States, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of pediatrics,song jiang central hospital,shanghai, China, department of pediatrics,the third affiliated hospital of zhengzhou university,zhengzhou,china,center for brain repair and rehabilitation,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of microbiology and immunology,institute of biomedicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of cancer immunology and aids,dana-farber cancer institute,harvard medical school,boston,ma,united states,department of microbiology and immunobiology,division of immunology,harvard medical school,boston,ma, United States, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of clinical sciences,east hospital,gothenburg,416 85,sweden,centre for the developing brain,department of perinatal imaging and health,king's college london,st. thomas' hospital,london,se1 7eh, United Kingdom, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30, Sweden, perinatal center,department of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg,se-405 30,sweden,department of pediatrics,the third affiliated hospital of zhengzhou university,zhengzhou, China
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Authors
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