Treatment of traumatic brain injury with thymosin β4 in rats

Xiong, Ye; Mahmood, Asim; Meng, Yuling; Zhang, Yanlu; Zhang, Zheng Gang; Morris, Daniel C.; Chopp, Michael

doi:10.3171/2010.4.jns10118

Cited by 68 publications

(87 citation statements)

References 70 publications

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“…We previously demonstrated a strong association of T␤4 treatment with OL differentiation in in vivo and in in vitro models (5)(6)(7)23). The results of this study further support our central hypothesis of T␤4-mediated oligodendrogenesis.…”

Section: Discussionsupporting

confidence: 85%

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Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

Santra

Zhang

Yang

et al. 2014

Journal of Biological Chemistry

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Background: Thymosin ␤4 (T␤4) promotes differentiation of oligoprogenitor cells (OPCs) to oligodendrocytes in animal models of neurological injury. Results: T␤4 increased expression of microRNA-146a and suppressed expression of TLR (Toll-like) proinflammatory cytokines. Conclusion: T␤4 suppresses the TLR proinflammatory pathway by up-regulating miR-146a to promote OPC differentiation. Signficance: Learning how T␤4 promotes oligodendrogenesis supports its development for clinical studies.

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Section: Discussionsupporting

confidence: 85%

“…In addition, T␤4 promotes cardiomyocyte and keratinocyte migration in these models. T␤4 improves functional outcome after experimental induction of multiple sclerosis, embolic stroke, and traumatic brain injury (5)(6)(7). In all three models, improvement in neurological outcome is associated with oligodendrogenesis (i.e.…”

Section: Thymosin ␤4 (T␤4)mentioning

confidence: 99%

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

Santra

Zhang

Yang

et al. 2014

Journal of Biological Chemistry

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“…Several recent studies have reported that treatments that protect or restore neurogenesis following TBI are associated with improved spatial learning [72][73][74][75]. Furthermore, Zhang et al [76] found that inhibition of neurogenesis with intraventricular cytosine arabinoside reversed the restorative effects of erythropoietin on post-TBI Morris Water maze performance.…”

Section: Discussionmentioning

confidence: 99%

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

2013

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The p75 neurotrophin receptor (p75 NTR ) influences the proliferation, survival, and differentiation of neuronal precursors and its expression is induced in injured brain, where it regulates cell survival. Here, we test the hypotheses that pharmacologic modulation of p75 NTR signaling will promote neural progenitor survival and proliferation, and improve outcomes of traumatic brain injury (TBI). LM11A-31, an orally available, blood-brain barrier-permeant small-molecule p75 NTR signaling modulator, significantly increased proliferation and survival, and decreased JNK phosphorylation, in hippocampal neural stem/progenitor cells in culture expressing wild-type p75 NTR , but had no effect on cells expressing a mutant neurotrophinunresponsive form of the receptor. The compound also enhanced the production of mature neurons from adult hippocampal neural progenitors in vitro. In vivo, intranasal administration of LM11A-31 decreased postinjury hippocampal and cortical neuronal death, neural progenitor cell death, gliogenesis, and microglial activation, and enhanced long-term hippocampal neurogenesis and reversed spatial memory impairments. LM11A-31 diminished the postinjury increase of SOX2-expressing early progenitor cells, but protected and increased the proliferation of endogenous polysialylated-neural cell adhesion molecule positive intermediate progenitors, and restored the long-term production of mature granule neurons. These findings suggest that modulation of p75 NTR actions using small molecules such as LM11A-31 may constitute a potent therapeutic strategy for TBI. STEM CELLS

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Section: Introductionmentioning

confidence: 99%

“…A number of studies have suggested that thymosin β4 is capable of promoting new blood vessel formation via stimulating the differentiation and directional migration of endothelial cells (17,18). These activities of thymosin β4 play an important role in dermal and corneal wound healing and in recovery from acute myocardial infarction and traumatic brain injury (11,(19)(20)(21).However, whether thymosin β4 is effective in alleviating inflammatory response and pancreatic tissue injury in SAP has not yet been elucidated. The present study investigated the effect of thymosin β4 on pancreatic injury following SAP, to identify whether it could be a good candidate for attenuating the severity of SAP.…”

mentioning

confidence: 99%

Effects of thymosin β4 on a rat model of severe acute pancreatitis

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effects of thymosin β4 on a rat model of severe acute pancreatitis (SAP) induced by sodium taurocholate (STC) and the underlying mechanism. SAP was induced by the retrograde infusion of 5% STC (1 ml/kg) into the bile-pancreatic duct. In certain rats, thymosin β4 (30 mg/kg) was administered intraperitoneally 30 min prior to the infusion of STC. The severity of pancreatitis was evaluated by the measurement of serum amylase, lipase, tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase (MPO) levels, and histological grading. Nuclear factor (NF)-κB activation was evaluated by immunohistochemistry and western blot analysis. Intercellular adhesion molecule (ICAM)-1 protein expression in the pancreas was studied using western blot analysis. Prophylactic administration of thymosin β4 was found to attenuate serum amylase and lipase activity and the serum concentrations of proinflammatory cytokines. In addition, it attenuated pathological pancreatic injury, pancreatic MPO activity, and the activation of NF-κB and ICAM-1 in the pancreas. These results suggest that thymosin β4 exerts a protective effect against STC-induced pancreatic injury. IntroductionAcute pancreatitis is an inflammatory disease of the pancreas characterized by acute abdominal pain and increased concentrations of serum amylase and lipase. In the majority of cases, it runs a mild course without complications. However, ~25% patients develop severe acute pancreatitis (SAP), which may result in systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome, and the mortality rate is up to 40% (1,2). In recent years, many investigators have attempted to reveal the pathogenesis of acute pancreatitis; however, the exact mechanisms are not well understood. Accumulating evidence indicates that SAP is closely associated with tissue injury and microcirculation disorders resulting from the production of proinflammatory cytokines and mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and intercellular adhesion molecule (ICAM)-1 (3,4). In addition, studies have shown that acute pancreatitis can lead to activation of the nuclear factor (NF)-κB signaling pathway (5,6). Therefore, reducing the levels of proinflammatory cytokines and adhesion molecules to block the inflammatory cascade may be a valid treatment strategy for acute pancreatitis.Thymosin β4 is a highly conserved polypeptide that was originally isolated from bovine thymus gland extract in 1981 (7). Thymosin β4 contains 43-amino acid residues with a molecular weight of 4964.5 Da and an isoelectric point of 4.6 (8). It is widely distributed in many tissues and cell types and is found in high concentrations in blood platelets, macrophages and white blood cells, but not in red blood cells (9). The most prominent physiological role of thymosin β4 as the major actin-sequestering peptide contributes to the regulation of actin polymerization in mammalian nucleated cells (10). There is g...

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Treatment of traumatic brain injury with thymosin β4 in rats

Cited by 68 publications

References 70 publications

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

Effects of thymosin β4 on a rat model of severe acute pancreatitis

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