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Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature
Kahriman A, Bouley J, Smith TW, Bosco DA, Woerman AL, Henninger N.. Acta neuropathologica communications, 2021-06-29
Topic: Brain proteins, microglia and lab models
Traumatic brain injury (TBI) constitutes one of the strongest environmental risk factors for several progressive neurodegenerative disorders of cognitive impairment and dementia that are characterized by the pathological accumulation of hyperphosphorylated tau (p-Tau). It has been questioned whether mouse closed-head TBI models can replicate human TBI-associated tauopathy. We conducted longitudinal histopathological characterization of a mouse closed head TBI model, with a focus on pathological features reported in human TBI-associated tauopathy. Male C57BL/6 J mice were subjected to once daily TBI for 5 consecutive days using a weight drop paradigm. Histological analyses (AT8, TDP-43, pTDP-43, NeuN, GFAP, Iba-1, MBP, SMI-312, Prussian blue, IgG, βAPP, alpha-synuclein) were conducted at 1 week, 4 weeks, and 24 weeks after rTBI and compared to sham operated controls. We conducted a systematic review of the literature for mouse models of closed-head injury focusing on studies referencing tau protein assessment. At 1-week post rTBI, p-Tau accumulation was restricted to the corpus callosum and perivascular spaces adjacent to the superior longitudinal fissure. Progressive p-Tau accumulation was observed in the superficial layers of the cerebral cortex, as well as in mammillary bodies and cortical perivascular, subpial, and periventricular locations at 4 to 24 weeks after rTBI. Associated cortical histopathologies included microvascular injury, neuroaxonal rarefaction, astroglial and microglial activation, and cytoplasmatic localization of TDP-43 and pTDP-43. In our systematic review, less than 1% of mouse studies (25/3756) reported p-Tau using immunostaining, of which only 3 (0.08%) reported perivascular p-Tau, which is considered a defining feature of chronic traumatic encephalopathy. Commonly reported associated pathologies included neuronal loss (23%), axonal loss (43%), microglial activation and astrogliosis (50%, each), and beta amyloid deposition (29%). Our novel model, supported by systematic review of the literature, indicates progressive tau pathology after closed head murine TBI, highlighting the suitability of mouse models to replicate pertinent human histopathology.
Key findings
- Histological analyses (AT8, TDP-43, pTDP-43, NeuN, GFAP, Iba-1, MBP, SMI-312, Prussian blue, IgG, βAPP, alpha-synuclein) were conducted at 1 week, 4 weeks, and 24 weeks after rTBI and compared to sham operated controls.
Why it matters
Mice given a closed head injury once daily for 5 consecutive days developed tau build-up that progressed over 1 to 24 weeks, including around blood vessels, a feature considered defining of chronic traumatic encephalopathy in people. A linked literature review found that less than 1% of mouse head-injury studies (25/3756) reported tau using immunostaining, and only 3 reported tau around blood vessels. The authors say the model replicates key human features, making it a useful tool for studying how head injury leads to tau disease, although these are mouse results.
Study details
- Study designsystematic review
- Effect size0.08%
- Evidence strengthHigh
How this study scored 59/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 52 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Nils Henninger: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Massachusetts Chan Medical School: institution h-index 990 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34187585) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-021-01220-8
- PubMed: 34187585
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Kahriman, A., Bouley, J., Smith, T. W., Bosco, D. A., Woerman, A. L., & Henninger, N. (2021). Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature. Acta neuropathologica communications. https://doi.org/10.1186/s40478-021-01220-8
Vancouver
Kahriman A, Bouley J, Smith TW, Bosco DA, Woerman AL, Henninger N. Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature. Acta neuropathologica communications. 2021. doi:10.1186/s40478-021-01220-8. PMID: 34187585.
BibTeX
@article{kahriman2021-34187585,
author = {Kahriman, A. and Bouley, J. and Smith, T. W. and Bosco, D. A. and Woerman, A. L. and Henninger, N.},
title = {{Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature}},
journal = {Acta neuropathologica communications},
year = {2021},
doi = {10.1186/s40478-021-01220-8},
pmid = {34187585},
url = {https://doi.org/10.1186/s40478-021-01220-8}
}
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