Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery

dc.contributor.authorKokiko-Cochran, Olga N.
dc.contributor.authorSaber, Maha
dc.contributor.authorPuntambekar, Shweta
dc.contributor.authorBemiller, Shane
dc.contributor.authorKatsumoto, Atsuko
dc.contributor.authorLee, Yu-Shang
dc.contributor.authorBhaskar, Kiran
dc.contributor.authorRansohoff, Richard M.
dc.contributor.authorLamb, Bruce T.
dc.contributor.departmentDepartment of Medical and Molecular Genetics, School of Medicineen_US
dc.date.accessioned2017-10-26T18:56:00Z
dc.date.available2017-10-26T18:56:00Z
dc.date.issued2017
dc.description.abstractTBI induces widespread neuroinflammation and accumulation of microtubule associated protein tau (MAPT) - two key pathological features of tauopathies. This study sought to characterize the microglial/macrophage response to TBI in genomic-based MAPT transgenic mice in a Mapt knockout background (called hTau). Two-month-old hTau and age-matched control male and female mice received a single lateral fluid percussion TBI or sham injury. Separate groups of mice were aged to an acute (3 days post-injury [DPI]) or chronic (135 DPI) post-injury time point. As judged by tissue immunostaining for macrophage markers, microglial/macrophage response to TBI was enhanced at 3 DPI in hTau mice compared to control TBI and sham mice. However, MAPT phosphorylation increased in hTau mice regardless of injury group. Flow cytometric analysis revealed distinct populations of microglia and macrophages within all groups at 135 DPI. Unexpectedly, microglial reactivity was significantly reduced in hTau TBI mice compared to all other groups. Instead, hTau TBI mice showed a persistent macrophage response. In addition, TBI enhanced MAPT pathology in the temporal cortex and hippocampus of hTau TBI mice compared to controls 135 DPI. A battery of behavioral test revealed that TBI in hTau mice resulted in compromised use of spatial search strategies to complete a water maze task despite lack of motor or visual deficits. Collectively, these data indicate that the presence of wild-type human tau alters the microglial/macrophage response to a single TBI, induces delayed, region-specific MAPT pathology, and alters cognitive recovery; however, the causal relationship between these events remains unclear. These results highlight the potential significance of communication between MAPT and microglia/macrophages following TBI and emphasize the role of neuroinflammation in post-injury recovery.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationKokiko-Cochran, O. N., Saber, M., Puntambekar, S., Bemiller, S. M., Katsumoto, A., Lee, Y.-S., … Lamb, B. T. (2017). Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery. Journal of Neurotrauma. https://doi.org/10.1089/neu.2017.5203en_US
dc.identifier.urihttps://hdl.handle.net/1805/14383
dc.language.isoenen_US
dc.publisherLieberten_US
dc.relation.isversionof10.1089/neu.2017.5203en_US
dc.relation.journalJournal of Neurotraumaen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjecttraumatic brain injuryen_US
dc.subjectmicrotube associated protein tauen_US
dc.subjectneuroinflammationen_US
dc.titleTraumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recoveryen_US
dc.typeArticleen_US
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