scholarly journals FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Chen ◽  
Xue Wang ◽  
Jian Hu ◽  
Jingting Du ◽  
Confidence Dordoe ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Protein Expression ◽  
Microvascular Endothelial Cell ◽  
Potential Candidate ◽  
Protective Effects ◽  
Junction Protein

Disruption of the blood-brain barrier (BBB) and the cerebral inflammatory response occurring after traumatic brain injury (TBI) facilitate further brain damage, which leads to long-term complications of TBI. Fibroblast growth factor 20 (FGF20), a neurotrophic factor, plays important roles in brain development and neuronal homeostasis. The aim of the current study was to assess the protective effects of FGF20 on TBI via BBB maintenance. In the present study, recombinant human FGF20 (rhFGF20) reduced neurofunctional deficits, brain edema, Evans blue extravasation and neuroinflammation in a TBI mouse model. In an in vitro TNF-α-induced human brain microvascular endothelial cell (HBMEC) model of BBB disruption, rhFGF20 reduced paracellular permeability and increased trans-endothelial electrical resistance (TEER). Both in the TBI mouse model and in vitro, rhFGF20 increased the expression of proteins composing in BBB-associated tight junctions (TJs) and adherens junctions (AJs), and decreased the inflammatory response, which protected the BBB integrity. Notably, rhFGF20 preserved BBB function by activating the AKT/GSK3β pathway and inhibited the inflammatory response by regulating the JNK/NFκB pathway. Thus, FGF20 is a potential candidate treatment for TBI that protects the BBB by upregulating junction protein expression and inhibiting the inflammatory response.

scholarly journals FGF20 protected against BBB disruption after traumatic brain injury by activating the AKT/GSK3β pathway to upregulate junction protein expression and inhibiting JNK/NFκB-dependent neuroinflammation

2019 ◽  
Author(s):  
Jun Chen ◽  
Xue Wang ◽  
Jian Hu ◽  
Wenting Huang ◽  
Confidence Dordoe ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Brain Edema ◽  
Microvascular Endothelial Cell ◽  
Potential Candidate ◽  
Protective Effects ◽  
Tnf Α ◽  
Junction Protein

Abstract Background ：Blood-brain barrier (BBB) disruption and the cerebral inflammatory response are two reciprocal mechanisms that work together to mediate the degree of brain edema, which is responsible for the majority of deaths after traumatic brain injury (TBI), and facilitate further brain damage, which leads to long-term TBI complications. Fibroblast growth factor 20 (FGF20), a neurotrophic factor, plays important roles in the development of dopaminergic neurons in Parkinson disease (PD). However, little is known about the role of FGF20 in TBI. The aim of the current study was to assess the protective effects of FGF20 in TBI through protecting the BBB. Methods: We explored the relationship between FGF20 and BBB function in controlled cortical impact (CCI)-induced TBI mice model and TNF-α-induced human brain microvascular endothelial cell (HBMEC) in vitro BBB disruption model. We also explored the mechanisms of these interactions and the signaling processes involved in BBB function and neuroinflammation. Results: In this study, we demonstrate that recombinant human FGF20 (rhFGF20) reduced neurofunctional deficits, brain edema and Evans Blue penetration in vivo after TBI. In an in vitro BBB disruption model of, rhFGF20 could reverse changes to TNF-α-induced HBMEC morphology, reduce Transwell permeability, and increase transendothelial electrical resistance (TEER). In both a TBI mouse model and in vitro , rhFGF20 upregulated the expression of BBB-associated tight junction (TJ) protein and adherens junction (AJ) protein via the AKT/GSK3β pathway. In addition, rhFGF20 inhibited the cerebral inflammatory response through regulating the JNK/NFκB pathway and further protected the function of the BBB. Conclusions : Our results contribute to a new treatment strategy in TBI research. FGF20 is a potential candidate to treat TBI as it protects the BBB via regulating the AKT/GSK3β and JNK/NFκB signaling pathways.

Protective Effects of N-Oleoylglycine in a Mouse Model of Mild Traumatic Brain Injury

2020 ◽  
Vol 11 (8) ◽  
pp. 1117-1128
Author(s):  
Fabiana Piscitelli ◽  
Francesca Guida ◽  
Livio Luongo ◽  
Fabio Arturo Iannotti ◽  
Serena Boccella ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury ◽  
Protective Effects

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 Lactobacillus rhamnosus GG Protects the Epithelial Barrier of Wistar Rats from the Pepsin-Trypsin-Digested Gliadin (PTG)-Induced Enteropathy

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1698 ◽  
Author(s):  
Antonella Orlando ◽  
Michele Linsalata ◽  
Giusy Bianco ◽  
Maria Notarnicola ◽  
Benedetta D’Attoma ◽  
...  
Keyword(s):  
Protein Expression ◽  
Wistar Rats ◽  
Lactobacillus Rhamnosus ◽  
Intercellular Junction ◽  
In Vivo Studies ◽  
Polyamine Metabolism ◽  
Protective Effects ◽  
Lactobacillus Rhamnosus Gg ◽  
Junction Protein

Celiac disease (CD) is a chronic immune-mediated disorder, characterized by enhanced paracellular permeability across the intestinal epithelium. The complex system of intercellular junctions, including tight junctions (TJs) and adherens junctions (AJs), seals together the epithelial cells to form a continuous layer. The improvements in barrier integrity have been related to modifications in intercellular junction protein expression. Polyamines (spermidine, spermine, and putrescine) actively participate in the modulation of the AJ expression. Both in vitro and in vivo studies have demonstrated that also probiotics can promote the integrity and the function of the intestinal barrier. On these bases, the present work investigated the protective effects exerted by Lactobacillus rhamnosus GG (L.GG) against the pepsin-trypsin-digested gliadin (PTG)-induced enteropathy in jejunal tissue samples of Wistar rats. In particular, the probiotic effects have been evaluated on the intestinal mucosal architecture, polyamine metabolism and intercellular junction protein expression (ZO-1, Occludin, Claudin-1, β-catenin and E-cadherin). The results from this study indicate that L.GG protects the intestinal mucosa of rats from PTG-induced damage, by preventing the reduction of the expression of the intercellular junction proteins. Consequently, a role for L.GG in the therapeutic management of the gluten-related disorders in humans could be hypothesized.

Protective Effect of Schisandrin on Hydrogen Peroxide-Induced Damage in PC12 Cells

2013 ◽  
Vol 750-752 ◽  
pp. 1545-1548
Author(s):  
Kuang Ren ◽  
Yan Chun Wang ◽  
Hong Yan Fan
Keyword(s):  
Protein Expression ◽  
Pc12 Cells ◽  
Antioxidant Properties ◽  
Immunocytochemical Staining ◽  
Potential Candidate ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Pre Treatment ◽  
Vitro Model

In this study, schisandrin was assessed for potential protective effects on pheochromocytoma cell line (PC12 cells). Using PC12 cells damage induced by H2O2(25μmol/L) as in vitro model. After pre-treatment with different concentration of schisandrin (0.3, 0.6, 1.2μM) for 24h, MTT assay was used to detect the cell viability, the supernatant of cells was collected to examine the levels of nitric oxide (NO) in each sample, and immunocytochemical staining was adopted to observe the expression levels of bcl-2. Results showed that schisandrin at different concentrations could increase the viability of PC12 cells and decrease the levels of NO in the culture medium. There were significant differences between schisandrin group and H2O2group (P<0.05,P<0.01). Immunocytochemical staining result revealed that schisandrin could upregulate bcl-2 protein expression. In summary, schisandrin shown significant neuroprotective effects on H2O2-injured PC12 cells through antioxidant properties and upregulate bcl-2 protein expression, and could be a potential candidate for intervention in neurodegenerative diseases.

Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 231-238 ◽  
Author(s):  
Hyejin Joo ◽  
Jinhyun Bae ◽  
Jun-Seon Lee ◽  
Yumi Bang ◽  
Beom-Joon Lee ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Body Weight ◽  
Brain Injury ◽  
Mouse Model ◽  
Brain Damage ◽  
Motor Function ◽  
Treated Group ◽  
Protective Effects ◽  
Object Recognition Test ◽  
Y Maze

AbstractEpimedii Herba (EH) has been used in traditional Asian medicine to treat hemiplegia following stroke. Icariin, its major active component, is used as a quality-control marker and for its various pharmacological effects. We hypothesized that icariin would show protective effects following traumatic brain injury (TBI). The TBI mouse model was induced using a controlled cortical impact method. Body weight, brain damage, motor function, and cognitive function were evaluated. Synaptogenesis markers were analyzed to investigate potential mechanisms of action. The animals were divided into six groups: sham, control, minocycline-treated group, and icariin-treated (3, 10, and 30 mg/kg, p. o.) groups. The icariin 30 mg/kg-treated group regained body weight at 7 and 8 d post TBI. Icariin 30 mg/kg- and 10 mg/kg-treated groups showed enhanced sensory-motor function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated groups showed increased recognition index in the novel object recognition test at all doses and increased spontaneous alternation in the Y-maze test at 30 mg/kg. Icariin upregulated brain-derived neurotrophic factor, synaptophysin and postsynaptic density protein 95 expressions. However, no protective effects against brain damage or neuronal death were observed. The current results provide a basis for using icariin following TBI and suggest that it could be a candidate for the development of therapeutic agents for functional recovery after TBI.

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 Protective Effects of Aquaporin-4 Deficiency on Longer-Term Neurological Outcomes in a Mouse Model of Traumatic Brain Injury

2020 ◽  
Author(s):  
Xiaosong Liu ◽  
Yingxin Xie ◽  
Xiangdong Wan ◽  
Jianliang Wu ◽  
Zhenzeng Fan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Water Channel ◽  
Amyloid Β ◽  
Aquaporin 4 ◽  
Protective Effects ◽  
Fluid Exchange ◽  
Glymphatic System ◽  
Neurological Outcomes

Abstract Background: Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear.Methods: AQP4−/− and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Morris water maze (MWM) was used to establish the cognitive functions of AQP4−/− and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay.Results: AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation.Conclusion: AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.

scholarly journals Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

2017 ◽  
Vol 42 (5) ◽  
pp. 1888-1896 ◽  
Author(s):  
Changmeng Cui ◽  
Jianzhong Cui ◽  
Feng Jin ◽  
Ying Cui ◽  
Ran Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Vitamin D ◽  
Cell Death ◽  
Brain Injury ◽  
Protein Expression ◽  
Rat Brain ◽  
Male Rats ◽  
Autophagic Flux ◽  
Sham Operation ◽  
Protective Effects

Background/Aims: Traumatic brain injury (TBI) is a major public health problem in the world and causes high rates of mortality and disability. Recent evidence suggests that vitamin D (VD) has neuroprotective actions and can promote function recovery after TBI. In vitro and in vivo studies have demonstrated that autophagy could be enhanced following supplementation with an active metabolite of VD (calcitriol). However, it is unclear whether autophagy participates in the protective effects of calcitriol after TBI. To test this hypothesis, we examined the protective effects of calcitriol on TBI-induced neurological impairment and further investigated whether calcitriol could modulate autophagy dysfunction-mediated cell death in the cortex region of rat brain. Methods: Eighty-five male rats (250-280 g) were randomly assigned to sham (n=15), TBI model (TBI, n=35) and calcitriol treatment (calcitriol, n=35) groups. Rats were injected intraperitoneally with calcitriol (1 µg/kg) at 30 min, 24 h and 48 h post-TBI in the calcitriol group. The lysosomal inhibitor, chloroquine (CQ), was used to evaluate autophagic flux in the TBI and calcitriol groups. Neurological functions were evaluated via the modified neurological severity score test at 1-7 days after TBI or sham operation, and the terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick-end labeling method was used to evaluate the ability of calcitriol to inhibit apoptosis. The expression of VDR, LC3 and p62 proteins was measured by western blot analysis at 1, 3 and 7 days post-injury Results: Calcitriol treatment attenuated mNSS at 2-7 days post-TBI (P < 0.05 versus TBI group). Calcitriol dramatically increased VDR protein expression compared with the untreated counterparts at 1, 3 and 7 days post-TBI (P < 0.05). The rate of apoptotic cells in calcitriol-treated rats was significantly reduced compared to that observed in the TBI group (P < 0.05). The LC3II/LC3I ratio was decreased in the cortex region at 1, 3 and 7 days post-TBI in rats treated with calcitriol (p < 0.05 versus TBI group), and the p62 expression was also attenuated (p < 0.05 versus TBI group). The LC3II/LC3I ratio in the calcitriol group was significantly increased when pretreated with CQ (P < 0.05). Conclusion: Calcitriol treatment activated VDR protein expression and attenuated neurological deficits in this rat TBI model. The protective effects might be associated with the restoration of autophagy flux and the decrease in apoptosis in the cortex region of rat brain.

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