Treatment of traumatic brain injury in rats with N-acetyl-seryl-aspartyl-lysyl-proline

Zhang, Yanlu; Zhang, Zheng Gang; Chopp, Michael; Meng, Yuling; Zhang, Li; Mahmood, Asim; Xiong, Ye

doi:10.3171/2016.3.jns152699

Cited by 39 publications

(26 citation statements)

References 90 publications

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“…These raise the possibility of therapy to improve the prognosis of acute TBI. Nevertheless, the 7 metabolites were assessed in previous study by offering each physiological and pathological understanding of TBI as a diagnostic tool [ 65 – 74 ]. By using our metabolomics platform in this study, these 7 plasma metabolites (statistically important with VIP >1.2) were assessed.…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomics profiles in rats with acute traumatic brain injury

et al. 2017

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Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. We validated the utility of plasma metabolomics analysis in the clinical diagnosis of acute TBI in a rat model of controlled cortical impact (CCI) using gas chromatography/mass spectrometry (GC/MS). Thirty Sprague-Dawley rats were randomly divided into two groups of 15 rats each: the CCI group and sham group. Blood samples were obtained from the rats within the first 24 h after TBI injury. GC/MS measurements were performed to evaluate the profile of acute TBI-induced metabolic changes, resulting in the identification of 45 metabolites in plasma. Principal component analysis, partial least squares-discriminant analysis, orthogonal partial least square discriminant analysis using hierarchical clustering and univariate/multivariate analyses revealed clear differences in the plasma metabolome between the acute CCI group and the sham group. CCI induced distinctive changes in metabolites including linoleic acid metabolism, amino acid metabolism, galactose metabolism, and arachidonic acid metabolism. Specifically, the acute CCI group exhibited significant alterations in proline, phosphoric acid, β-hydroxybutyric acid, galactose, creatinine, L-valine, linoleic acid and arachidonic acid. A receiver operating characteristic curve analysis showed that the above 8 metabolites in plasma could be used as the potential biomarkers for the diagnosis of acute TBI. Furthermore, this study is the first time to identify the galactose as a biomarker candidate for acute TBI. This comprehensive metabolic analysis complements target screening for potential diagnostic biomarkers of acute TBI and enhances predictive value for the therapeutic intervention of acute TBI.

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Section: Discussionmentioning

confidence: 99%

Plasma metabolomics profiles in rats with acute traumatic brain injury

et al. 2017

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“…Then, Tβ4 acts as a reservoir for the unpolymerized actin within the mammalian cells to release them when it is needed. The role of Tβ4 has proved to be essential for neurons given its function as an anti-inflammatory and neuroprotective peptide [102][103][104][105]. Polymerization of actin filaments.…”

Section: Formation and Remodeling Of Actin Filamentsmentioning

confidence: 99%

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Muñoz-Lasso

Romá‐Mateo

Pallardó

et al. 2020

Cells

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Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.

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“…The modified MWM test was used to assess spatial learning function, as previously described. 10,61 This test was performed daily for 5 days on all rats 3 months after injury (i.e., on days 86-90) (for details, see Supplemental Information).…”

Section: Mwm Testmentioning

confidence: 99%

Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury

Zhang¹,

Chopp

Zhang

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Cerebrolysin is a neuropeptide preparation that mimics the properties of neurotrophic factors and has had beneficial effects in the treatment of neurodegenerative diseases, stroke, and traumatic brain injury (TBI). To further evaluate treatment schemes, the authors assessed the dose-response of Cerebrolysin on functional improvement in a rat model of mild TBI (mTBI). METHODS This dose-response study was a prospective, randomized, blinded, and placebo-controlled preclinical experiment. Male Wistar adult rats, subjected to mTBI induced by a closed head impact, were treated randomly with 0 (saline as placebo), 0.8, 2.5, or 7.5 ml/kg of Cerebrolysin 4 hours after mTBI and daily for a total of 10 consecutive days. A battery of cognitive and sensorimotor functional tests was performed over 90 days. RESULTS The primary outcome was functional improvement over the 90 days; animal weight and death were the secondary and safety outcomes, respectively. A significant (p < 0.001) dose effect of Cerebrolysin on cognitive recovery 3 months after injury was found. Cerebrolysin at a dose of ≥ 0.8 ml/kg significantly (p < 0.001) improved cognitive outcome. The higher dose (7.5 ml/kg) resulted in significantly better cognitive recovery than the lowest doses (0.8 ml/kg) but not relative to the 2.5-ml/kg dose. Cerebrolysin at a dose of 2.5 or 7.5 ml/kg also caused different onset times of significant improvement in sensorimotor function. No differences in body weight or mortality rate among the groups were found. CONCLUSIONS This preclinical randomized, placebo-controlled, and blinded study with a clinically relevant treatment scheme revealed that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after mTBI and then once daily for a total of 10 consecutive days, improved functional outcomes 3 months after injury. A dose of 2.5 ml/kg is likely an optimal dose for the treatment of experimental mTBI.

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Treatment of traumatic brain injury in rats with N-acetyl-seryl-aspartyl-lysyl-proline

Cited by 39 publications

References 90 publications

Plasma metabolomics profiles in rats with acute traumatic brain injury

Plasma metabolomics profiles in rats with acute traumatic brain injury

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury

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