The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy

Anthony L. Petraglia, Rochester Regional HealthFollow
Benjamin A. Plog, Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Samantha Dayawansa, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Matthew L. Dashnaw, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Katarzyna Czerniecka, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Corey T. Walker, Division of Neurological Surgery, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Michael Chen, Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Ollivier Hyrien, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, USA.
Jeffrey J. Iliff, Department of Anesthesiology and Peri-operative Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Rashid Deane, Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Jason H. Huang, Department of Neurosurgery, Baylor Scott and White Health System, Temple, Texas, USA.
Maiken Nedergaard, Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.

Department

Neurosurgery

Document Type

Article

Publication Title

Surgical neurology international

Abstract

BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. METHODS: Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. RESULTS: Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. CONCLUSIONS: The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

First Page

184

DOI

10.4103/2152-7806.147566

Volume

5

Publication Date

1-17-2015

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