Evaluation of Neuronal Protective Effects of Xanthine Oxidoreductase Inhibitors on Severe Whole-brain Ischemia in Mouse Model and Analysis of Xanthine Oxidoreductase Activity in the Mouse Brain

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

Download Full-text

Moderate hypoxia induces xanthine oxidoreductase activity in arterial endothelial cells

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2005.11.008 ◽

2006 ◽

Vol 40 (6) ◽

pp. 952-959 ◽

Cited By ~ 49

Author(s):

Eric E. Kelley ◽

Thomas Hock ◽

Nicholas K.H. Khoo ◽

Gloria R. Richardson ◽

Kamorris K. Johnson ◽

...

Keyword(s):

Endothelial Cells ◽

Xanthine Oxidoreductase ◽

Oxidoreductase Activity ◽

Moderate Hypoxia ◽

Arterial Endothelial Cells

Download Full-text

Gabapentin Neuroprotection and Seizure Suppression in Immature Mouse Brain Ischemia

Pediatric Research ◽

10.1203/pdr.0b013e318174e70e ◽

2008 ◽

Vol 64 (1) ◽

pp. 81-85 ◽

Cited By ~ 30

Author(s):

Beatrix S Traa ◽

Justin D Mulholland ◽

Shilpa D Kadam ◽

Michael V Johnston ◽

Anne M Comi

Keyword(s):

Mouse Brain ◽

Brain Ischemia ◽

Immature Mouse ◽

Seizure Suppression

Download Full-text

Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia

Brain Research ◽

10.1016/j.brainres.2012.12.006 ◽

2013 ◽

Vol 1495 ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

Yingzhu Chen ◽

Qiong Yi ◽

Gang Liu ◽

Xue Shen ◽

Lihui Xuan ◽

...

Keyword(s):

White Matter ◽

Brain Ischemia ◽

Myelin Sheath ◽

White Matter Injury ◽

Cerebral White Matter ◽

Whole Brain

Download Full-text

Brain Metabolomics Study on the Protective Effects of Ginsenosides Rg1 and Rb1 in an Alzheimer’s Disease Mouse Model

Pharmaceutical Analytical Chemistry Open Access ◽

10.4172/2471-2698.1000108 ◽

2015 ◽

Vol 01 (01) ◽

Author(s):

Naijing Li

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Protective Effects ◽

Metabolomics Study

Download Full-text

A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

Vaccines ◽

10.3390/vaccines9121400 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1400

Author(s):

Dennis Imhof ◽

William Robert Pownall ◽

Camille Monney ◽

Anna Oevermann ◽

Andrew Hemphill

Keyword(s):

Listeria Monocytogenes ◽

Mouse Model ◽

Neospora Caninum ◽

Post Partum ◽

Systemic Infection ◽

Surface Protein ◽

Control Group ◽

Protective Effects ◽

Igg Antibody ◽

Th2 Response

The apicomplexan parasite Neospora caninum is the worldwide leading cause of abortion and stillbirth in cattle. An attenuated mutant Listeria monocytogenes strain (Lm3Dx) was engineered by deleting the virulence genes actA, inlA, and inlB in order to avoid systemic infection and to target the vector to antigen-presenting cells (APCs). Insertion of sag1, coding for the major surface protein NcSAG1 of N. caninum, yielded the vaccine strain Lm3Dx_NcSAG1. The efficacy of Lm3Dx_NcSAG1 was assessed by inoculating 1 × 105, 1 × 106, or 1 × 107 CFU of Lm3Dx_NcSAG1 into female BALB/c mice by intramuscular injection three times at two-week intervals, and subsequent challenge with 1 × 105N. caninum tachyzoites of the highly virulent NcSpain-7 strain on day 7 of pregnancy. Dose-dependent protective effects were seen, with a postnatal offspring survival rate of 67% in the group treated with 1 × 107 CFU of Lm3Dx_NcSAG1 compared to 5% survival in the non-vaccinated control group. At euthanasia (25 days post-partum), IgG antibody titers were significantly decreased in the groups receiving the two higher doses and cytokines recall responses in splenocyte culture supernatants (IFN-γ, IL-4, and IL-10) were increased in the vaccinated groups. Thus, Lm3Dx_NcSAG1 induces immune-protective effects associated with a balanced Th1/Th2 response in a pregnant neosporosis mouse model and should be further assessed in ruminant models.

Download Full-text

Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.678377 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhidan Li ◽

Wei Zhang ◽

Fang Luo ◽

Jian Li ◽

Wenbin Yang ◽

...

Keyword(s):

Mouse Model ◽

Protective Effect ◽

Airway Inflammation ◽

Lung Tissue ◽

Immunoglobulin E ◽

Allergic Airway Inflammation ◽

Treg Cells ◽

Protective Effects ◽

Novel Therapy ◽

Allergen Sensitization

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.

Download Full-text