scholarly journals Salivary gland extract from the deer tick, Ixodes scapularis, facilitates neuroinvasion by Powassan virus in BALB/c mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rodrigo I. Santos ◽  
Meghan E. Hermance ◽  
Erin S. Reynolds ◽  
Saravanan Thangamani

AbstractPowassan virus (POWV) is a neuroinvasive flavivirus transmitted to mammals by the bite of ixodid ticks. In this study, we sought to investigate the impact of tick salivary gland extract (SGE) on POWV neuroinvasion. BALB/c mice were footpad inoculated with either a high dose or a low dose of POWV, with and without Ixodes scapularis salivary gland extract. Brain and spinal cord were extracted daily, and immunohistochemical techniques were used for temporal tracking of POWV antigen. The temporal pattern of POWV staining showed a caudal to rostral spread of POWV in the brains of mice from both high dose infection groups. For the high dose infection groups, the presence of tick SGE did not influence the spread of POWV in the brain. Mice infected with the low dose of virus alone did not present POWV staining in the brain; however, in the presence of SGE, low dose infected mice presented scattered foci of POWV-infected cells throughout the brain. This study shows that tick SGE facilitates POWV neuroinvasion when mice are infected with the lower dose of POWV. We also found two patterns of central nervous system invasion that were directly influenced by the dose of POWV administered.

Author(s):  
Melissa Carolina Pereira ◽  
Elen Fernanda Nodari ◽  
Marina Rodrigues de Abreu ◽  
Lisiery Negrini Paiatto ◽  
Patrícia Ucelli Simioni ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


2003 ◽  
Vol 77 (24) ◽  
pp. 13323-13334 ◽  
Author(s):  
Yang Wang ◽  
Mario Lobigs ◽  
Eva Lee ◽  
Arno Müllbacher

ABSTRACT C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ling Chen ◽  
Jerry B Lingrel ◽  
John M Hamlyn ◽  
Mordecai P Blaustein

Dietary salt is a major factor in the pathogenesis of essential hypertension (EH), but the underlying links are unresolved. Animal models indicate that angiotensin (Ang) II and high dietary salt (HS) are convergent signals that act via the brain to elevate blood pressure (BP). Low-dose sc Ang II+HS is a common model for EH. We tested the Na + pump ouabain binding site’s role in this model because it is crucial in some other hypertension models (e.g., ACTH and Nedd4-2-knockout +HS). Mice that express Na + pumps with a mutant, ouabain-resistant α2 catalytic subunit (α2 R/R ; cation transport is normal), and wild type (WT), ouabain sensitive controls (α2 S/S ) were studied. [80-90% of rodent artery myocyte Na + pumps are ouabain-resistant (α1 R/R ); only 10-20% are α2.] BP was measured by telemetry. First, 3 basal 24 hr BPs were recorded. Osmotic 4-week minipumps were then implanted sc in all mice to deliver vehicle (saline; Expt. #1,3), or 400 (Expt. #1,2) or 800 (Expt. #3) ng/kg/min Ang II; simultaneously, in Expt. #2, the diet was switched from 0.4% (standard) to 2% NaCl (HS). BPs were monitored every 3-4 days for up to 4 weeks. Also, in Expt. #2, on day 21, all mice received 2 ip injections, 4 hrs apart, of 10 mg/kg DigiFab, Fab fragments that immuno-neutralize ouabain, while BP was continuously monitored; on day 23, the mice received 2 ip injections of CroFab, anti-crotalus toxin (‘control’) Fab fragments. Results: 1. Basal mean BP (MBP) was 10±2 mm Hg higher in α2 R/R than in WT mice ( P <0.01; n =21 & 29; ANOVA). 2. In WT mice, 400 ng/kg/min sc Ang II and Ang II+HS raised MBP by 15±1 and 34±1 mm Hg, respectively ( P <0.01; n =7-8; ANOVA). 3. The MPB elevation in Ang II+HS α2 R/R (17±2 mm Hg) was only half that in WT mice ( P <0.01; n =7 each; ANOVA). 4. DigiFab rapidly (<1 hr) reduced MBP by 14±2 mm Hg in Ang II+HS hypertensive WT mice ( P <0.001; n =7; T-test), but not in α2 R/R mice ( P <0.01; n =7 each; ANOVA); CroFab did not lower MBP in either strain. 5. 800 ng/kg/min sc Ang II elevated systolic BP by 55±3 mm Hg in WT mice, but by only 37±3 mm Hg in α2 R/R mice ( P <0.05; n =3-5; ANOVA). Conclusions: Ouabain-sensitive α2 Na + pumps and their endogenous ligand are both required for full expression of low-dose Ang II-salt hypertension. Ouabain-sensitive α2 pumps apparently also contribute to high-dose Ang II-hypertension.


Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 182 ◽  
Author(s):  
Rafaelli de Souza Gomes ◽  
Kely Navegantes-Lima ◽  
Valter Monteiro ◽  
Ana de Brito Oliveira ◽  
Dávila Rodrigues ◽  
...  

Sepsis is a systemic disease with life-threatening potential and is characterized by a dysregulated immune response from the host to an infection. The organic dysfunction in sepsis is associated with the production of inflammatory cascades and oxidative stress. Previous studies showed that Aedes aegypti saliva has anti-inflammatory, immunomodulatory, and antioxidant properties. Considering inflammation and the role of oxidative stress in sepsis, we investigated the effect of pretreatment with salivary gland extract (SGE) from Ae. aegypti in the induction of inflammatory and oxidative processes in a murine cecum ligation and puncture (CLP) model. Here, we evaluated animal survival for 16 days, as well as bacterial load, leukocyte migration, and oxidative parameters. We found that the SGE pretreatment improved the survival of septic mice, reduced bacterial load and neutrophil influx, and increased nitric oxide (NO) production in the peritoneal cavity. With regard to oxidative status, SGE increased antioxidant defenses as measured by Trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH), while reducing levels of the oxidative stress marker malondialdehyde (MDA). Altogether, these data suggest that SGE plays a protective role in septic animals, contributing to oxidative and inflammatory balance during sepsis. Therefore, Ae. aegypti SGE is a potential source for new therapeutic molecule(s) in polymicrobial sepsis, and this effect seems to be mediated by the control of inflammation and oxidative damage.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S216-S217
Author(s):  
Chao Ma ◽  
Yan Wu ◽  
Pei Chen ◽  
Yuan Jia ◽  
Dongqing Yin ◽  
...  

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.


2019 ◽  
Vol 301 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Mauricio La Rosa ◽  
Chasey Omere ◽  
Tiffany Redfern ◽  
Mahmoud Abdelwahab ◽  
Nicholas Spencer ◽  
...  

BIO-PROTOCOL ◽  
2017 ◽  
Vol 7 (14) ◽  
Author(s):  
Michael Schmid ◽  
Elizabeth Kauffman ◽  
Anne Payne ◽  
Eva Harris ◽  
Laura Kramer

2002 ◽  
Vol 70 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Amy R. Tvinnereim ◽  
Sara E. Hamilton ◽  
John T. Harty

ABSTRACT Understanding how existing antivector immunity impacts live vaccine delivery systems is critical when the same vector system may be used to deliver different antigens. We addressed the impact of antivector immunity, elicited by immunization with attenuated actA-deficient Listeria monocytogenes, on the CD8+-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinant L. monocytogenes. Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocytogenes generated similar numbers of CD8+ T cells specific for the NP118-126 epitope. High-dose immunization with actA-deficient L. monocytogenes resulted in substantial numbers of CD8+ T cells specific for the L. monocytogenes LLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinant L. monocytogenes resulted in rapid control of the infection and decreased CD8+-T-cell responses against both the secreted and nonsecreted form of the recombinant antigen compared to the response of naïve mice. In contrast, mice immunized with a low dose of actA-deficient L. monocytogenes had ∼10-fold fewer effector and memory T cells specific for LLO91-99 and a substantially higher CD8+-T-cell response against the recombinant antigen after challenge with recombinant L. monocytogenes. Although mice immunized with low-dose actA-deficient L. monocytogenes had a substantial recall response to LLO91-99, which reached the same levels by 5 to 7 days postchallenge as that in high-dose-immunized mice, they exhibited decreased ability to control L. monocytogenes replication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.


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