Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury

Cheng, Wai Hang; Cheung, Honor; Kang, Amy; Fan, Jianjia; Cooper, Jennifer; Anwer, Mehwish; Barron, Carlos; Wilkinson, Anna; Hu, Grace; Yue, Jefferey; Cripton, Peter A.; Vocadlo, David J.; Wellington, Cheryl L.

doi:10.1101/2022.09.01.506145

Cited by 2 publications

(7 citation statements)

References 81 publications

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“…t-Tau was assessed at ‘days’ in 5 studies (41,68,72,95,98) and p-Tau in 3 studies (41,72,98). t-Tau was assessed at ‘weeks’ in 2 studies (98,100) and p-Tau in 1 study (98). t-Tau was assessed at ‘months’ in 1 study (100) and p-Tau in 1 study (88) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…t-Tau was assessed at ‘weeks’ in 2 studies (98,100) and p-Tau in 1 study (98). t-Tau was assessed at ‘months’ in 1 study (100) and p-Tau in 1 study (88) ( Fig. 4A ).…”

Section: Resultsmentioning

confidence: 99%

“…Data in the chronic phase post-injury are scarce, but a progressive increase was observed following moderate- to-severe TBI ( Fig. 4A ) (98,100) and rmTBI ( Fig. 4C ) (46,87,89,93), but not after smTBI ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…4A ). Following moderate-to-severe TBI, there was an acute increase in t-Tau within hours of TBI (68,95,101), and these levels remained elevated at weeks post-injury (98,100). For p-Tau, there was a slower increase in p-Tau starting within days of TBI (72,98), with a steady increase in p-Tau in the weeks (98) and months (88) post-injury.…”

Section: T-tau and P-taumentioning

confidence: 99%

“…Biomarker kinetics. In moderate-to-severe TBI models, circulating t-Tau levels were assessed at 'hours' in 9 studies(50,68,72,82,95,98,(100)(101)(102) and circulating pTau levels in 2 studies(72,98). t-Tau was assessed at 'days' in 5 studies(41,68,72,95,98) and p-Tau in 3 studies(41,72,98).…”

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confidence: 99%

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Translating from mice to humans: using preclinical blood-based biomarkers for the prognosis and treatment of traumatic brain injury

Lisi,

Moro,

Mazzone

et al. 2023

Preprint

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Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing potential new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%, perhaps due, in part, to distinct timescales of pathophysiological processes in rodents versus humans that impedes translational advancements. Incorporating clinically relevant biomarkers in preclinical studies may provide an opportunity to calibrate preclinical models to human TBI biomechanics and pathophysiology. To support this important translational goal, we conducted a systematic literature review of preclinical TBI studies in rodents measuring blood levels of clinically used NfL, t-Tau, p-Tau, UCH-L1, or GFAP, published in PubMed/MEDLINE up to June 13th, 2023. We focused on blood biomarker temporal trajectories and their predictive and pharmacodynamic value and discuss our findings in the context of the latest clinical TBI biomarker data. Out of 369 original studies identified through the literature search, 71 met the inclusion criteria, with a median quality score on the CAMARADES checklist of 5 (interquartile range 4-7). NfL was measured in 17 preclinical studies, GFAP in 41, t-Tau in 17, p-Tau in 7, and UCH-L1 in 19 preclinical studies. Data in rodent models show that all blood biomarkers exhibited injury severity-dependent elevations, with GFAP and UCH-L1 peaking within hours after TBI, NfL peaking within days after TBI and remaining elevated up to 6 months post-injury, whereas t-Tau and p-Tau levels were gradually increased many weeks after TBI. Blood NfL levels emerges as a prognostic indicator of white matter loss after TBI, while both NfL and GFAP hold promise for pharmacodynamic studies of neuroprotective treatments. Therefore, blood-based preclinical biomarker trajectories could serve as important anchor points that may advance translational research in the TBI field. However, further investigation into biomarker levels in the subacute and chronic phases will be needed to more clearly define pathophysiological mechanisms and identify new therapeutic targets for TBI.

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Section: Resultsmentioning

confidence: 99%

“…t-Tau was assessed at ‘weeks’ in 2 studies (98,100) and p-Tau in 1 study (98). t-Tau was assessed at ‘months’ in 1 study (100) and p-Tau in 1 study (88) ( Fig. 4A ).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: T-tau and P-taumentioning

confidence: 99%

mentioning

confidence: 99%

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Translating from mice to humans: using preclinical blood-based biomarkers for the prognosis and treatment of traumatic brain injury

Lisi,

Moro,

Mazzone

et al. 2023

Preprint

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Effectiveness and mechanisms of combined use of antioxidant nutrients in protecting against oxidative stress‐induced neuronal loss and related neurological deficits

Wang,

Wei,

Sun

et al. 2024

CNS Neurosci Ther

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BackgroundOxidative stress is a well‐known pathological factor driving neuronal loss and age‐related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress‐induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo.MethodsMouse neuroblastoma Neuro‐2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK‐8 assay. Eight‐week‐old male mice were intraperitoneally injected with D‐(+)‐galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms.ResultsExposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D‐(+)‐galactose‐induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety‐ and depression‐like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment.ConclusionsThese results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress‐mediated neuronal loss and brain dysfunction due to age‐related neurodegenerative conditions.

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Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury

Cited by 2 publications

References 81 publications

Translating from mice to humans: using preclinical blood-based biomarkers for the prognosis and treatment of traumatic brain injury

Translating from mice to humans: using preclinical blood-based biomarkers for the prognosis and treatment of traumatic brain injury

Effectiveness and mechanisms of combined use of antioxidant nutrients in protecting against oxidative stress‐induced neuronal loss and related neurological deficits

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