scholarly journals Rh-relaxin-2 Attenuates Degranulation of mast cells by Inhibiting NF-κB through PI3K-AKT/TNFAIP3 Pathway in an Experimental Germinal Matrix Hemorrhage Rat Model

2020 ◽  
Author(s):  
Peng Li ◽  
Gang Zhao ◽  
Fanfan Chen ◽  
Yan Ding ◽  
Tianyi Wang ◽  
...  
Keyword(s):  
Mast Cells ◽  
Rat Model ◽  
Protective Effects ◽  
Nissl Staining ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage ◽  
Pi3k Inhibitor Ly294002 ◽  
Neurobehavioral Function ◽  
Phosphorylated Akt ◽  
Relaxin 2

Abstract Background: Mast cells play an important role in early immune reactions in the brain by inducing degranulation and releasing inflammatory mediators. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a GMH rat model. Methods: One hundred and sixty-four P7 rat pups were subjected to germinal matrix hemorrhage (GMH) by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 hours prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 hour and 12 hours after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injections. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and Toluidine staining. Results: Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6 and TNF-α. However, knockdown of RXFP1 and PI3K abolished the protective effects of rh-relaxin-2. Conclusions: Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.

scholarly journals Protective Effects of Liu Wei Di Huang Wan on the Liver, Orbitofrontal Cortex Nissl Bodies, and Neurites in MSG+PH-Induced Liver Regeneration Rat Model

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bin-Bin Zhao ◽  
Qing-hua Long ◽  
Chao-yang Wang ◽  
Lin-lin Chen ◽  
Guang-jing Xie ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Rat Model ◽  
Orbitofrontal Cortex ◽  
Monosodium Glutamate ◽  
Serum Levels ◽  
Saline Group ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Nissl Staining ◽  
Suspension Array

Introduction. To examine the protective effects of Liu Wei Di Huang Wan formula (LWDH) on liver and orbitofrontal cortex (OFC) injuries in monosodium glutamate (MSG) and partial hepatectomy (PH) rat model. Methods. Neonatal Wistar rats were given MSG or saline on postnatal days 2, 4, 6, 8, and 10. The rats were caged into five groups and treated accordingly at six weeks old as follows: Saline group, Saline+PH group, MSG group, MSG+PH group, and LWDH group (MSG+PH+LWDH). The PH was performed during week 8 by excision of the left and median hepatic lobes (occupying about 68% of whole liver).On day 8 after the PH, the rats were subjected to an inner OFT before being sacrificed. The liver and OFC were stained using H&E, ORO, or Nissl staining. The expression of neurotrophic factors (β-NGF, BDNF) was examined in the OFC lysates by ELISA. Serum levels of cytokines (IL-1β, VEGF) were examined using the Bio-Plex suspension array. Results. LWDH increased the total distance traveled by the animals (p<0.05), and LWDH improved the integrity of the Nissl bodies in the OFC (mean area of the Nissl bodies, p<0.01; mean diameter, p<0.05; mean density, p<0.05; and IOD, p<0.01). There were less white area in the liver (p>0.05) and decreased hepatic steatosis (p<0.01) in LWDH group. LWDH administration decreased the expression of serum levels of IL-1β (p>0.05), while it increased VEGF (p>0.05) expression. LWDH administration increased the expression of BDNF (p>0.05) and β-NGF (p>0.05) in the OFC, all as compared to the MSG+PH group. Conclusion. LWDH partly protected the animals from depressive-like behaviors in the MSG+PH-induced liver regeneration neonatal rat model. LWDH alleviated hepatic injury and steatosis and, furthermore, protected the Nissl body integrity and the growth of neurites.

scholarly journals Secukinumab attenuates reactive astrogliosis via IL‐17RA/(C/EBPβ)/SIRT1 pathway in a rat model of germinal matrix hemorrhage

2019 ◽  
Vol 25 (10) ◽  
pp. 1151-1161 ◽  
Author(s):  
Sheng‐Peng Liu ◽  
Lei Huang ◽  
Jerry Flores ◽  
Yan Ding ◽  
Peng Li ◽  
...  
Keyword(s):  
Rat Model ◽  
Germinal Matrix ◽  
Reactive Astrogliosis ◽  
Germinal Matrix Hemorrhage

scholarly journals Anti-inflammation conferred by stimulation of CD200R1 via Dok1 pathway in rat microglia after germinal matrix hemorrhage

2017 ◽  
Vol 39 (1) ◽  
pp. 97-107 ◽  
Author(s):  
Zhanhui Feng ◽  
Lan Ye ◽  
Damon Klebe ◽  
Yan Ding ◽  
Zhen-Ni Guo ◽  
...  
Keyword(s):  
Western Blot ◽  
Tnf Alpha ◽  
Protective Effects ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage ◽  
Beneficial Effects ◽  
Cd200 Receptor ◽  
Rat Pups ◽  
Enhanced Expression ◽  
Time Dependent Effect

CD200 has been reported to be neuroprotective in neurodegenerative diseases. However, the potential protective effects of CD200 in germinal matrix hemorrhage (GMH) have not been investigated. We examined the anti-inflammatory mechanisms of CD200 after GMH. A total of 167 seven-day-old rat pups were used. The time-dependent effect of GMH on the levels of CD200 and CD200 Receptor 1 (CD200R1) was evaluated by western blot. CD200R1 was localized by immunohistochemistry. The short-term (24 h) and long-term (28 days) outcomes were evaluated after CD200 fusion protein (CD200Fc) treatment by neurobehavioral assessment. CD200 small interfering RNA (siRNA) and downstream of tyrosine kinase 1 (Dok1) siRNA were injected intracerebroventricularly. Western blot was employed to study the mechanisms of CD200 and CD200R1. GMH induced significant developmental delay and caused impairment in both cognitive and motor functions in rat pups. CD200Fc ameliorated GMH-induced damage. CD200Fc increased expression of Dok1 and decreased IL-1beta and TNF-alpha levels. CD200R1 siRNA and Dok1 siRNA abolished the beneficial effects of CD200Fc, as demonstrated by enhanced expression levels of IL-1beta and TNF-alpha. CD200Fc inhibited GMH-induced inflammation and this effect may be mediated by CD200R1/Dok1 pathway. Thus, CD200Fc may serve as a potential treatment to ameliorate brain injury for GMH patients.

Activation of PI3K–Akt through taurine is critical for propofol to protect rat cardiomyocytes from doxorubicin-induced toxicity

2014 ◽  
Vol 92 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Xuechao Sun ◽  
Jing Gu ◽  
Meng Chi ◽  
Mingming Li ◽  
Shi Lei ◽  
...  
Keyword(s):  
Critical Role ◽  
Chemotherapeutic Agents ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Simultaneous Treatment ◽  
Rat Cardiomyocytes ◽  
Pi3k Inhibitor Ly294002 ◽  
Phosphorylated Akt ◽  
Cellular Apoptosis ◽  
Induced Changes

Myocardial toxicity is one of the major side effects of many chemotherapeutics. It has been shown that propofol can ameliorate the cardiotoxicity of chemotherapeutic agents. In this study, we intend to investigate the role of the PI3K–Akt–Bad signaling pathway in propofol relief of doxorubicin-induced oxidative stress and apoptosis in rat cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with vehicle, doxorubicin, propofol, or propofol plus doxorubicin in the presence or absence of the PI3K inhibitor LY294002. Cells were harvested 20 h post-exposure to doxorubicin followed by analysis of their cellular taurine content, oxidative/nitrative stresses, and cellular apoptosis. The activation of the PI3K–Akt pathway was analyzed by immunoblotting. FACS, TUNEL, and LDH assays showed that the viability of cardiomyocytes was markedly reduced by doxorubicin, but was improved by propofol. Doxorubicin treatment significantly elevated cellular reactive oxygen and nitrogen contents while lowering the levels of taurine, Akt, and phosphorylated Akt and Bad. The abovementioned doxorubicin-induced changes were reversed by propofol. The protective effects of propofol were abrogated by simultaneous treatment with LY294002. In conclusion, the PI3K–Akt–Bad pathway plays a critical role in conferring the protective effects of propofol against myocardial toxicity from doxorubicin.

scholarly journals Bliverdin reductase-A improves neurological function in a germinal matrix hemorrhage rat model

2018 ◽  
Vol 110 ◽  
pp. 122-132 ◽  
Author(s):  
Yiting Zhang ◽  
Yan Ding ◽  
Tai Lu ◽  
Yixin Zhang ◽  
Ningbo Xu ◽  
...  
Keyword(s):  
Rat Model ◽  
Neurological Function ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage
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