RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury
| العنوان: | RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury |
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| المؤلفون: | Carsten Culmsee, Igor Khalin, Peter Vandenabeele, Marco Duering, Nicole A. Terpolilli, Antonia Wehn, Nikolaus Plesnila, Farida Hellal |
| المصدر: | Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-18 (2021) Acta Neuropathologica Communications ACTA NEUROPATHOLOGICA COMMUNICATIONS |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Hippocampus, ACTIVATION, HEMORRHAGE, Mice, Traumatic brain injury, Brain Injuries, Traumatic, Brain Injury, Chronic, Medicine and Health Sciences, DECOMPRESSIVE, Medicine, Chronic posttraumatic brain damage, Cerebral Cortex, Mice, Knockout, Neurons, CEREBRAL MICROBLEEDS, Neurodegeneration, NEURODEGENERATION, Brain, Neuroprotection, medicine.anatomical_structure, Hindlimb Suspension, Receptor-Interacting Protein Serine-Threonine Kinases, Necroptosis, Microglia, medicine.symptom, Astrocyte, Magnetic, CRANIECTOMY, POSTTRAUMATIC HYDROCEPHALUS, Brain damage, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Magnetic resonance imaging, INFLAMMATION, Memory, Animals, Ferroptosis, Maze Learning, RC346-429, resonance imaging, business.industry, Research, Biology and Life Sciences, IN-VITRO, medicine.disease, CONTROLLED CORTICAL IMPACT, Barnes maze, FERROPTOSIS, Astrocytes, Neurology (clinical), Neurology. Diseases of the nervous system, business, Neuroscience, Protein Kinases |
| الوصف: | Traumatic brain injury (TBI) causes acute and subacute tissue damage, but is also associated with chronic inflammation and progressive loss of brain tissue months and years after the initial event. The trigger and the subsequent molecular mechanisms causing chronic brain injury after TBI are not well understood. The aim of the current study was therefore to investigate the hypothesis that necroptosis, a form a programmed cell death mediated by the interaction of Receptor Interacting Protein Kinases (RIPK) 1 and 3, is involved in this process. Neuron-specific RIPK1- or RIPK3-deficient mice and their wild-type littermates were subjected to experimental TBI by controlled cortical impact. Posttraumatic brain damage and functional outcome were assessed longitudinally by repetitive magnetic resonance imaging (MRI) and behavioral tests (beam walk, Barnes maze, and tail suspension), respectively, for up to three months after injury. Thereafter, brains were investigated by immunohistochemistry for the necroptotic marker phosphorylated mixed lineage kinase like protein(pMLKL) and activation of astrocytes and microglia. WT mice showed progressive chronic brain damage in cortex and hippocampus and increased levels of pMLKL after TBI. Chronic brain damage occurred almost exclusively in areas with iron deposits and was significantly reduced in RIPK1- or RIPK3-deficient mice by up to 80%. Neuroprotection was accompanied by a reduction of astrocyte and microglia activation and improved memory function. The data of the current study suggest that progressive chronic brain damage and cognitive decline after TBI depend on the expression of RIPK1/3 in neurons. Hence, inhibition of necroptosis signaling may represent a novel therapeutic target for the prevention of chronic post-traumatic brain damage. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01236-0. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4582c5f2a4fc59c30274d89677ddce19Test https://doaj.org/article/a7508595efbf478288b4b0d810f4d914Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4582c5f2a4fc59c30274d89677ddce19 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
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