Endogenous TGFβ1 Plays a Crucial Role in Functional Recovery After Traumatic Brain Injury Associated with Smad3 Signal in Rats

Wang, Xuyang; Ba, Ying-Chun; Xiong, Liu‐Lin; Li, Xiaoli; Zou, Yu; Zhu, Ye-Chun; Zhou, Xin‐Fu; Wang, Ting‐Hua; Wang, Fang; Huang, Tian; Li, Jintao

doi:10.1007/s11064-015-1634-x

Cited by 17 publications

(12 citation statements)

References 42 publications

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“…TGF-β is another pleiotropic cytokine with immunoregulatory properties that is found in CSF of TBI patients (Csuka et al, 1999; Morganti-Kossmann et al, 1999). Following weight drop TBI in rats, TGF-β1 was expressed in pericontusional neurons and astrocytes (Wang et al, 2015). Knockdown of TGF-β1 in the pericontusional area using a shRNA approach resulted in increased neuronal cell death, reduced astrogliosis, and enhanced neurological deficits.…”

Section: Introductionmentioning

confidence: 99%

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Jassam

Izzy

Whalen

et al. 2017

Neuron

562

496

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SUMMARY Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as “secondary injury”. Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follows TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states towards a stimulus and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

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Section: Introductionmentioning

confidence: 99%

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Jassam

Izzy

Whalen

et al. 2017

Neuron

562

496

View full text Add to dashboard Cite

show abstract

“…TGF-β1 knockdown reduced the number of neurons, inhibited astrogliosis and lead to a significant neurological deficit in rats with TBI. Subsequently, Smad3, a downstream signaling molecule of TGF-β1 receptor, was reported to participate in pericontusional region post-TBI (Wang X.Y. et al, 2015) Cumulatively these evidences support the claim of the neuroprotective role of TGF-β in cerebral IRI.…”

Section: Introductionmentioning

confidence: 78%

Anti-inflammatory Effects of Traditional Chinese Medicines on Preclinical in vivo Models of Brain Ischemia-Reperfusion-Injury: Prospects for Neuroprotective Drug Discovery and Therapy

et al. 2019

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Acquired brain ischemia-and reperfusion-injury (IRI), including both Ischemic stroke (IS) and Traumatic Brain injury (TBI), is one of the most common causes of disability and death in adults and represents a major burden in both western and developing countries worldwide. China’s clinical neurological therapeutic experience in the use of traditional Chinese medicines (TCMs), including TCM-derived active compounds, Chinese herbs, TCM formulations and decoction, in brain IRI diseases indicated a trend of significant improvement in patients’ neurological deficits, calling for blind, placebo-controlled and randomized clinical trials with careful meta-analysis evaluation. There are many TCMs in use for brain IRI therapy in China with significant therapeutic effects in preclinical studies using different brain IRI-animal. The basic hypothesis in this field claims that in order to avoid the toxicity and side effects of the complex TCM formulas, individual isolated and identified compounds that exhibited neuroprotective properties could be used as lead compounds for the development of novel drugs. China’s efforts in promoting TCMs have contributed to an explosive growth of the preclinical research dedicated to the isolation and identification of TCM-derived neuroprotective lead compounds. Tanshinone, is a typical example of TCM-derived lead compounds conferring neuroprotection toward IRI in animals with brain middle cerebral artery occlusion (MCAO) or TBI models. Recent reports show the significance of the inflammatory response accompanying brain IRI. This response appears to contribute to both primary and secondary ischemic pathology, and therefore anti-inflammatory strategies have become popular by targeting pro-inflammatory and anti-inflammatory cytokines, other inflammatory mediators, reactive oxygen species, nitric oxide, and several transcriptional factors. Here, we review recent selected studies and discuss further considerations for critical reevaluation of the neuroprotection hypothesis of TCMs in IRI therapy. Moreover, we will emphasize several TCM’s mechanisms of action and attempt to address the most promising compounds and the obstacles to be overcome before they will enter the clinic for IRI therapy. We hope that this review will further help in investigations of neuroprotective effects of novel molecular entities isolated from Chinese herbal medicines and will stimulate performance of clinical trials of Chinese herbal medicine-derived drugs in IRI patients.

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“…The long-term presence of TGF-β after injury is associated with clinical improvement (Ma et al, 2008). TGF-β promotes neuronal differentiation and survival after a stroke and prevents the loss of neural cells and consequent functional harm in a TBI model (Wang et al, 2015). Increasing of TGF-β expression by P. acnes was described since 1995 by Masuhara (1995) that demonstrated elevated levels in the liver of injected rats after P. acnes treatment.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Mesenchymal Stem Cell Immunomodulatory Properties by Heat-Killed Propionibacterium acnes via TLR2

Silveira

Ishimura

Teixeira

et al. 2019

Front. Mol. Neurosci.

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Mesenchymal stem cells (MSCs) are an essential tool for regenerative medicine, which aims to develop new technologies to improve their effects to obtain useful transplantation results. MSC immunomodulatory role has been just demonstrated; however, how they react when they are stimulated by an adjuvant is poorly understood. Our group showed the adjuvant effect of killed Propionibacterium acnes (P. acnes) on hematopoietic stem cells. As these cells share the same MSCs bone marrow (BM) site and interact with each other, here we evaluated the P. acnes and its soluble polysaccharide (PS) effect on MSCs and their immunomodulatory role in a murine model of traumatic brain injury (TBI). The bacteria increased the absolute number of MSCs, including MSC subpopulations, and maintained MSC plasticity. P. acnes and PS enhanced MSC proliferation and improved their immunomodulatory effect. P. acnes-MSC and PS-MSC transplantation increased anti-inflammatory cytokine expression and diminished pro-inflammatory cytokine expression after injury. This effect seemed to be mediated via TLR2 since P. acnes-KOTLR2-MSC transplantation decreased TGF-β and IL-10 expression. Increasing in neural stem cells and neuroblasts after PS-MSC transplantation was also observed. The adjuvant effect of P. acnes is an alternative means of expanding MSCs and important to identify their subpopulations to know better their role under exogenous stimuli including inflammation resolution in an experimental model.

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Endogenous TGFβ1 Plays a Crucial Role in Functional Recovery After Traumatic Brain Injury Associated with Smad3 Signal in Rats

Cited by 17 publications

References 42 publications

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Anti-inflammatory Effects of Traditional Chinese Medicines on Preclinical in vivo Models of Brain Ischemia-Reperfusion-Injury: Prospects for Neuroprotective Drug Discovery and Therapy

Improvement of Mesenchymal Stem Cell Immunomodulatory Properties by Heat-Killed Propionibacterium acnes via TLR2

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