SynthesisExperimental neurology2020
The effects of mild closed head injuries on tauopathy and cognitive deficits in rodents: Primary results in wild type and rTg4510 mice, and a systematic review.
Synthesis in Experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- 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 · 2021Pooled it
- IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity.Science advances · 2026Article
- Chronic Neurobehavioral and Neuropathological Consequences of Repeated Blast Exposure in P301S Transgenic Tau Rats.Neurotrauma reports · 2025Article
- Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice.NeuroImage · 2024Article
- Chronic traumatic encephalopathy pathognomonic lesions occurring in isolation adjacent to infiltrative and non-infiltrative white matter lesions.Journal of neuropathology and experimental neurology · 2024Article
- Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache.Cephalalgia : an international journal of headache · 2023Article
- Fixed Time-Point Analysis Reveals Repetitive Mild Traumatic Brain Injury Effects on Resting State Functional Magnetic Resonance Imaging Connectivity and Neuro-Spatial Protein Profiles.Journal of neurotrauma · 2023Article
- Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice.Acta neuropathologica · 2023Article
- Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury.International journal of molecular sciences · 2023Article
- Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study.Neuropsychology · 2023Observational
- Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice.Journal of visualized experiments : JoVE · 2022Article
- Repetitive Mild Closed Head Injury in Adolescent Mice Is Associated with Impaired Proteostasis, Neuroinflammation, and Tauopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Lateral Fluid Percussion Injury Causes Sex-Specific Deficits in Anterograde but Not Retrograde Memory.Frontiers in behavioral neuroscience · 2022Article
- Intranasal delivery of exosomes from human adipose derived stem cells at forty-eight hours post injury reduces motor and cognitive impairments following traumatic brain injury.Neurochemistry international · 2021Article
- Progressive long-term spatial memory loss following repeat concussive and subconcussive brain injury in mice, associated with dorsal hippocampal neuron loss, microglial phenotype shift, and vascular abnormalities.The European journal of neuroscience · 2021Article
- Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review.Acta neuropathologica communications · 2021Review
- Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice.International journal of molecular sciences · 2021Article
- Magnetic Resonance Imaging in Tauopathy Animal Models.Frontiers in aging neuroscience · 2021Review
- Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
In humans, the majority of sustained traumatic brain injuries (TBIs) are classified as 'mild' and most often a result of a closed head injury (CHI). The effects of a non-penetrating CHI are not benign and may lead to chronic pathology and behavioral dysfunction, which could be worsened by repeated head injury. Clinical-neuropathological correlation studies provide evidence that conversion of tau into abnormally phosphorylated proteotoxic intermediates (p-tau) could be part of the pathophysiology triggered by a single TBI and enhanced by repeated TBIs. However, the link between p-tau and CHI in rodents remains controversial. To address this question experimentally, we induced a single CHI or two CHIs to WT or rTg4510 mice. We found that 2× CHI increased tau phosphorylation in WT mice and rTg4510 mice. Behavioral characterization in WT mice found chronic deficits in the radial arm water maze in 2× CHI mice that had partially resolved in the 1× CHI mice. Moreover, using Manganese-Enhanced Magnetic Resonance Imaging with R1 mapping - a novel functional neuroimaging technique - we found greater deficits in the rTg4510 mice following 2× CHI compared to 1× CHI. To integrate our findings with prior work in the field, we conducted a systematic review of rodent mild repetitive CHI studies. Following Prisma guidelines, we identified 25 original peer-reviewed papers. Results from our experiments, as well as our systematic review, provide compelling evidence that tau phosphorylation is modified by experimental mild TBI studies; however, changes in p-tau levels are not universally reported. Together, our results provide evidence that repetitive TBIs can result in worse and more persistent neurological deficits compared to a single TBI, but the direct link between the worsened outcome and elevated p-tau could not be established.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.