Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice.

Autor: Izzy S; Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA.; Harvard Medical School, Boston, MA 02115, USA., Brown-Whalen A; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA., Yahya T; Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA., Sarro-Schwartz A; Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA., Jin G; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA., Chung JY; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA., Lule S; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA., Morsett LM; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA., Alquraini A; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA.; Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia., Wu L; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA., Hickman SE; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA., Whalen MJ; Harvard Medical School, Boston, MA 02115, USA.; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA., El Khoury J; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA.; Harvard Medical School, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Jan 18; Vol. 22 (2). Date of Electronic Publication: 2021 Jan 18.
DOI: 10.3390/ijms22020907
Abstrakt: Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.
Databáze: MEDLINE
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