Xintong Ge1, Jinwen Yu2, Shan Huang2, Zhenyu Yin2, Zhaoli Han2, Fanglian Chen3, Zengguang Wang4, Jianning Zhang5, Ping Lei6. 1. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. 2. Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China. 3. Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. 4. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. Electronic address: zgwang@tmu.edu. 5. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. Electronic address: jnzhang@tmu.edu. 6. Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: plei@tmu.edu.
Abstract
BACKGROUND: Athletes, military personnel and mobility-declined elderly people are prone to repetitive mild traumatic brain injury (rmTBI). The injury does not cause acute pathological changes, but leads to chronic neurodegeneration, long-term cognitive dysfunction and even chronic traumatic encephalopathy (CTE). Many existing rmTBI animal models reported uncontrollable adverse effects and long experiment period. Therefore, an improved model needs to be designed. NEW METHOD: Our rmTBI mouse model is a modification of the closed head injury method using electronic controlled cortical impact system. Discontinuous 4 impacts with 48-h interval were performed. A key facet of the model is the use of our designed molded acrylic cast and concave metal disc (as a helmet). They could scatter and transmit hitting power to the whole brain, thus produced a mild diffused injury. The procedure does not require scalp incision or craniotomy, which allows the impacting to be completed in 2 min. RESULTS: Our model did not induce acute macroscopic brain damage and brain edema. It could lead to sustained neuroinflammation and chronic neurodegeneration in injured brain, and resulted in cognitive dysfunction within 5 weeks post-injury. COMPARISON WITH EXISTING METHODS: Previously reported adverse effects including skull fractures, hemorrhage and brain tissue loss were not observed in our model. An experiment period of 5 weeks was allowed for observing chronic neurodegeneration and cognitive dysfunction. CONCLUSIONS: Our model is beneficial to use for simplicity, reproducibility and time saver. It could serve as a platform for research on the pathogenesis, diagnosis and potential therapeutics for rmTBI and CTE.
BACKGROUND: Athletes, military personnel and mobility-declined elderly people are prone to repetitive mild traumatic brain injury (rmTBI). The injury does not cause acute pathological changes, but leads to chronic neurodegeneration, long-term cognitive dysfunction and even chronic traumatic encephalopathy (CTE). Many existing rmTBI animal models reported uncontrollable adverse effects and long experiment period. Therefore, an improved model needs to be designed. NEW METHOD: Our rmTBI mouse model is a modification of the closed head injury method using electronic controlled cortical impact system. Discontinuous 4 impacts with 48-h interval were performed. A key facet of the model is the use of our designed molded acrylic cast and concave metal disc (as a helmet). They could scatter and transmit hitting power to the whole brain, thus produced a mild diffused injury. The procedure does not require scalp incision or craniotomy, which allows the impacting to be completed in 2 min. RESULTS: Our model did not induce acute macroscopic brain damage and brain edema. It could lead to sustained neuroinflammation and chronic neurodegeneration in injured brain, and resulted in cognitive dysfunction within 5 weeks post-injury. COMPARISON WITH EXISTING METHODS: Previously reported adverse effects including skull fractures, hemorrhage and brain tissue loss were not observed in our model. An experiment period of 5 weeks was allowed for observing chronic neurodegeneration and cognitive dysfunction. CONCLUSIONS: Our model is beneficial to use for simplicity, reproducibility and time saver. It could serve as a platform for research on the pathogenesis, diagnosis and potential therapeutics for rmTBI and CTE.
Authors: Fabio A Vigil; Eda Bozdemir; Vladislav Bugay; Sang H Chun; MaryAnn Hobbs; Isamar Sanchez; Shayne D Hastings; Rafael J Veraza; Deborah M Holstein; Shane M Sprague; Chase M Carver; Jose E Cavazos; Robert Brenner; James D Lechleiter; Mark S Shapiro Journal: J Cereb Blood Flow Metab Date: 2019-07-04 Impact factor: 6.200
Authors: Rachael S Allen; Cara T Motz; Anayesha Singh; Andrew Feola; Lauren Hutson; Amber Douglass; Sriganesh Ramachandra Rao; Lara A Skelton; Lidia Cardelle; Katie L Bales; Kyle Chesler; Kaavya Gudapati; C Ross Ethier; Matthew M Harper; Steven J Fliesler; Machelle T Pardue Journal: Vision Res Date: 2021-07-30 Impact factor: 1.886