The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Kobeissy, Firas; Mallah, Khalil; Zibara, Kazem; Dakroub, Fatima; Dalloul, Zeinab; Nasser, Mohamad; Nasrallah, Leila; Mallah, Zahraa; El-Achkar, Ghewa A.; Ramadan, Naify; Mohamed, Wael; Mondello, Stefania; Hamade, Eva; Habib, Aı̈da

doi:10.1016/j.neuint.2022.105301

Cited by 1 publication

(10 citation statements)

References 49 publications

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“…In moderate-to-severe TBI models, circulating UCH-L1 was assessed at ‘hours’ in 15 studies (57–59,62,64,65,70,71,74,75,104–108), at ‘days’ in 7 studies (57,70,73,75,85,104,105), and at ‘weeks’ in 1 study (73) ( Fig. 4A ).…”

Section: Resultsmentioning

confidence: 99%

“…Finally, circulating UCH-L1 levels are modestly impacted by TBI, even after severe TBI in rodents, where UCH-L1 shows a marginal increase early after injury (Fig. 4A) (57,59,64,65,69,71,75,85,104,105,131),…”

Section: Discussionmentioning

confidence: 96%

“…Value as a pharmacodynamic biomarker. The pharmacodynamic value of GFAP was assessed in 17 preclinical studies (41,(57)(58)(59)62,65,67,70,71,73,74,78,82,85,86,89,93) using various injury severity models. Different therapeutic approaches were evaluated and ranged from lifestyle interventions (67,73,86), to anti-epileptic drugs, (41,59) to immunomodulatory agents (57,62,82).…”

Section: Gfapmentioning

confidence: 99%

“…Different therapeutic approaches were evaluated and ranged from lifestyle interventions (67,73,86), to anti-epileptic drugs, (41,59) to immunomodulatory agents (57,62,82). TBI-induced blood GFAP levels were decreased in 9 out of 13 studies from moderate-to-severe TBI (57,59,67,74,78,85,89), smTBI (73), and rmTBI (93) models.…”

Section: Gfapmentioning

confidence: 99%

“…Asterisks indicate that age had to be inferred from the animal weight reported.Biomarker kinetics. In moderate-to-severe TBI models, circulating UCH-L1 was assessed at 'hours' in 15 studies(57)(58)(59)62,64,65,70,71,74,75,(104)(105)(106)(107)(108), at 'days' in 7 studies(57,70,73,75,85,104,105), and at 'weeks' in 1 study…”

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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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%

Section: Discussionmentioning

confidence: 96%

Section: Gfapmentioning

confidence: 99%

Section: Gfapmentioning

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

Self Cite

View full text Add to dashboard Cite

show abstract

The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Cited by 1 publication

References 49 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

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