scholarly journals Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury

2020 ◽  
Author(s):  
xiaobing long ◽  
Xiaolong Yao ◽  
Qian Jiang ◽  
Yiping Yang ◽  
Xuejun He ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Vital Role ◽  
Neurological Deficits ◽  
Inflammatory Factors ◽  
Protective Mechanism ◽  
Vitro Model ◽  
Phenotype Transformation

Abstract Background: The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as potent mediators involved in intercellular communication. Methods: In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and edema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot, and electron microscopy. A mouse model of TBI and an in vitro model of lps-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p-overexpressing in TBI-induced nerve injury.Results: We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the mNSS score and attenuated brain injury in a strictly controlled cortical impact mouse model. Conclusions: Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-kB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.

scholarly journals Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury

2019 ◽  
Author(s):  
xiaobing long ◽  
Xiaolong Yao ◽  
Qian Jiang ◽  
Yiping Yang ◽  
Xuejun He ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Vital Role ◽  
Neurological Deficits ◽  
Inflammatory Factors ◽  
Protective Mechanism ◽  
Vitro Model ◽  
Phenotype Transformation

Abstract Background: The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as potent mediators involved in intercellular communication. Methods: In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and edema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot, and electron microscopy. A mouse model of TBI and an in vitro model of lps-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p-overexpressing in TBI-induced nerve injury. Results: We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the mNSS score and attenuated brain injury in a strictly controlled cortical impact mouse model. Conclusions: Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-kB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.

scholarly journals The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Fangxia Guan ◽  
Tuanjie Huang ◽  
Xinxin Wang ◽  
Qu Xing ◽  
Kristyn Gumpper ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Therapeutic Efficacy ◽  
Brain Dysfunction ◽  
Vital Role ◽  
Neurological Deficits ◽  
Human Umbilical Cord

Abstract Background Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. Methods In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. Results We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling. Conclusion MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.

scholarly journals Hydrogen exerts neuroprotection by activation of the miR‐21/PI3K/AKT/GSK‐3β pathway in an in vitro model of traumatic brain injury

2020 ◽  
Vol 24 (7) ◽  
pp. 4061-4071 ◽  
Author(s):  
Lu Wang ◽  
Zhenyu Yin ◽  
Feng Wang ◽  
Zhaoli Han ◽  
Yifeng Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Vitro Model ◽  
Gsk 3Β

scholarly journals Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

2020 ◽  
Author(s):  
Jingtao Wu ◽  
Caimei He ◽  
Jie Bu ◽  
Yue Luo ◽  
Shuyuan Yang ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Vital Role ◽  
Inflammatory Factors ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Epithelial Barriers ◽  
Vitro Model

Abstract Background：The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model. Results: The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1µg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription- polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

In vitro model of traumatic brain injury to screen neuro-regenerative biomaterials

2021 ◽  
pp. 112253
Author(s):  
Raja Haseeb Basit ◽  
Nikolaos Tzerakis ◽  
Stuart Iain Jenkins ◽  
Divya Maitreyi Chari
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Vitro Model

S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury

2015 ◽  
Vol 40 (5) ◽  
pp. 991-999 ◽  
Author(s):  
Valentina Di Pietro ◽  
Angela Maria Amorini ◽  
Giacomo Lazzarino ◽  
Kamal Makram Yakoub ◽  
Serafina D’Urso ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
In Vitro Model ◽  
Acidic Protein ◽  
Vitro Model

scholarly journals Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model

2018 ◽  
Vol 35 (8) ◽  
pp. 1037-1044 ◽  
Author(s):  
Rita Campos-Pires ◽  
Mariia Koziakova ◽  
Amina Yonis ◽  
Ashni Pau ◽  
Warren Macdonald ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Vitro Model

Fluid percussion barotrauma chamber: A new in vitro model for traumatic brain injury

1991 ◽  
Vol 51 (5) ◽  
pp. 417-424 ◽  
Author(s):  
Scott R. Shepard ◽  
Jamshid B.G. Ghajar ◽  
Roseanne Giannuzzi ◽  
Susan Kupferman ◽  
Robert J. Hariri
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Fluid Percussion ◽  
Vitro Model

Neuroprotective properties of xenon and helium in an in vitro model of traumatic brain injury: One small step or one big jump?*

2008 ◽  
Vol 36 (2) ◽  
pp. 647-648
Author(s):  
Vincenzo Fodale ◽  
Letterio B. Santamaria ◽  
Giovanni Grasso
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Small Step ◽  
Vitro Model

scholarly journals Dual effects of thyroid hormone on neurons and neurogenesis in traumatic brain injury

2020 ◽  
Vol 11 (8) ◽  
Author(s):  
Chao Lin ◽  
Nan Li ◽  
Hanxiao Chang ◽  
Yuqi shen ◽  
Zheng Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Thyroid Hormone ◽  
Glucose Deprivation ◽  
Neurological Deficits ◽  
Neuron Culture ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Mature Neurons

Abstract Thyroid hormone (TH) plays a crucial role in neurodevelopment, but its function and specific mechanisms remain unclear after traumatic brain injury (TBI). Here we found that treatment with triiodothyronine (T3) ameliorated the progression of neurological deficits in mice subjected to TBI. The data showed that T3 reduced neural death and promoted the elimination of damaged mitochondria via mitophagy. However, T3 did not prevent TBI-induced cell death in phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (Pink1) knockout mice suggesting the involvement of mitophagy. Moreover, we also found that T3 promoted neurogenesis via crosstalk between mature neurons and neural stem cells (NSCs) after TBI. In neuron cultures undergoing oxygen and glucose deprivation (OGD), conditioned neuron culture medium collected after T3 treatment enhanced the in vitro differentiation of NSCs into mature neurons, a process in which mitophagy was required. Taken together, these data suggested that T3 treatment could provide a therapeutic approach for TBI by preventing neuronal death via mitophagy and promoting neurogenesis via neuron–NSC crosstalk.

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