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Advanced Neurology

REVIEW ARTICLE
Cerebral tau pathology in murine models of

closed-head traumatic brain injury: A narrative
review and comparison with human disease

Elif O. Dogan * , Aydan Kahriman 2 , Muhammed E. Gunduz 1 , and
1
Nils Henninger 1,3
1 Department of Neurology, University of Massachusetts Chan Medical School, Worcester,
Massachusetts, United States of America
2 Department of Neurology, SUNY Upstate Medical University, Syracuse, New York, United States
of America
3 Department of Psychiatry, University of Massachusetts Chan Medical School, Worcester,
Massachusetts, United States of America

Abstract
Traumatic brain injury (TBI) constitutes a significant public health problem, as a
leading cause of death and disability worldwide. Epidemiological evidence indicates
that TBI is a major risk factor for several neurodegenerative disorders characterized
by the pathological accumulation of the tubulin-associated unit (tau) protein. To
delineate the underlying mechanisms promoting tau pathology following TBI,
murine models are increasingly utilized as they provide the ability to conduct
detailed histopathological analyses under well-controlled conditions. Closed-
*Corresponding author: skull TBI models are frequently employed to mimic the most common type of TBI
Elif O. Dogan encountered in clinical settings; however, relatively few studies have examined tau
(elifozgedogan@gmail.com)
pathology in these models. In this review, we aim to summarize the current data
Citation: Dogan EO, Kahriman A, on tau pathologies observed in murine models of closed-head TBI and compare
Gunduz ME, Henninger N. Cerebral
tau pathology in murine models of them with human disease. In summary, murine TBI models replicate many important
closed-head traumatic brain injury: aspects of tau pathology seen in human TBI. This includes phosphorylation of tau
A narrative review and comparison protein at similar sites as in human tau, accumulation of hyperphosphorylated tau
with human disease. Adv Neuro.
2024;3(3):3213. (pTau) in both neurons and astrocytes, formation of tau oligomers, presence of pTau
doi: 10.36922/an.3213 in similar cerebral locations as in human TBI, and the deregulation of similar tau-
Received: March 20, 2024 related kinases and phosphatases (e.g., glycogen synthase kinase-3, p38 mitogen-
activated protein kinase, c-Jun N-terminal kinase, and protein phosphatase-2B).
Accepted: May 27, 2024 Nevertheless, the formation of paired helical filaments and neurofibrillary tangles
Published Online: August 23, 2024 appears to be limited to tau transgenic models.
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the Keywords: Axonal injury; Brain trauma; Chronic traumatic encephalopathy; Concussion;
Creative Commons Attribution Tau oligomers; Neurodegeneration; Neurofibrillary tangles; Transgenic
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited. 1. Introduction
Publisher’s Note: AccScience
Publishing remains neutral with Traumatic brain injury (TBI) is a leading cause of death and disability, impacting
regard to jurisdictional claims in 1
published maps and institutional approximately 70 million individuals globally each year, resulting in significant long-
2,3
affiliations. term disabilities and a high burden on patients, caregivers, and the health-care system.

Volume 3 Issue 3 (2024) 1 doi: 10.36922/an.3213