Effect of Bacteriophage-Derived Double Stranded RNA on Rat Peritoneal Macrophages and Microglia in Normoxia and Hypoxia

Pjanova, Dace; Hurmach, Yevheniia; Rudyk, Mariia; Khranovska, N.; Skachkova, O.; Verhovcova, Irina; Skivka, Larysa

doi:10.2478/prolas-2021-0050

Cited by 4 publications

(1 citation statement)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microglia cell isolation. Microglial cells were isolated from whole brain tissue homogenates as described earlier [18]. For this purpose, animal brains were rapidly excised on ice and homogenized in icecold phosphate buffered saline (PBS) supplemented with 0.2 % glucose using a Potter homogenizer.…”

Section: Methodsmentioning

confidence: 99%

Pro-inflammatory effects of placebo neurosurgery in rats: age-related features

et al. 2022

View full text Add to dashboard Cite

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, affecting millions of people globally and causing significant disability and mortality. Animal models are the final step in completing preclinical studies and the most appropriate approach for gaining a thorough understanding of disease pathophysiology. Modeling of idiopathic AD and PD in rodents requires stereotactic injections of disease‑triggering substances. The placebo surgery group is an integral component of the design of these experiments in order to diminish study bias as a result of animal stress and non‑specific surgical impact. Inflammation is the most commonly reported non‑specific post‑surgery phenomenon, which can manifest in different ways in animals of different ages used in these experiments. Objective — to compare the long‑term pro‑inflammatory effects of placebo surgery, commonly employed for PD and AD modeling, in rats of different ages. Materials and methods. Adult male Wistar rats aged 4 and 14 months were used in the study. The placebo surgery consisted of a stereotactic unilateral intracerebral infusion of buffer solution. Before the placebo surgery, animals were anaesthetized using ketamine or xylazine administered intraperitoneally. Intact animals of both ages were used as a control. The evaluation of pro‑inflammatory effects of placebo surgery was conducted using biomarkers of local and systemic inflammation: metabolic polarization of phagocytes (microglia, peripheral blood cells), C‑reactive protein (CRP) plasma level, and systemic inflammation indexes calculated from the hemogram study. Results. In young lesioned animals, a pronounced pro‑inflammatory functional shift of microglia and signs of the resolution of systemic inflammation (an anti‑inflammatory skew of circulating phagocyte metabolism as compared to age‑matched intact controls) were observed in the long term after the placebo neurosurgery. In old intact animals, hematological and immunological markers of low‑grade systemic inflammation were observed. In lesioned old rats, residual neuroinflammation along with pronounced systemic inflammatory responses (leukocytosis, substantially increased SIRI and SII values, pro‑inflammatory metabolic shift of peripheral blood phagocytes as compared to age‑matched intact controls) were registered. Conclusions. The effects of placebo neurosurgical manipulations in rats depend on age. Meta‑inflammation inherent to aged rats is aggravated by non‑specific post‑surgery inflammation, leading to pronounced, persistent systemic inflammatory responses.

show abstract

Section: Methodsmentioning

confidence: 99%

Pro-inflammatory effects of placebo neurosurgery in rats: age-related features

et al. 2022

View full text Add to dashboard Cite

show abstract

Long-Term Effects of Sham Surgery on Phagocyte Functions in Rats

Oliynyk¹

2022

Biotechnol. acta

View full text Add to dashboard Cite

Animal models of inflammatory disorders, including those of the nervous system are commonly used to explore the pathophysiological role of immune cell response in disease triggering and course and to develop biotechnology products for therapeutic use. Modeling some of these disorders, particularly neurodegenerative diseases, implies surgical manipulations for the intracerebral introduction of disease-initiating substances (toxins, amyloids etc.). Design of these experiments involves the use of sham-operated animals as a control of non-specific intrinsic side-effects elicited by surgical manipulations per se, including local and systemic inflammation, where phagocytic cells are key participants. Short-term post-surgical immunomodulatory effects are widely reported. However, no study thus far has examined the long term effects of sham-surgery on phagocyte functions. The purpose of this study was to evaluate the effect of sham-surgery, commonly used for modeling neurodegenerative diseases, on phagocyte functions in the far terms after the surgical manipulations. Materials and Methods. Adult male Wistar rats were used in the study. Sham surgery consisted of stereotactic unilateral injection of saline solution into the median forebrain bundle (sham-operated 1, SO1) or directly into the substantia nigra (sham-operated 2, SO2). Before the placebo surgery, animals were anaesthetized using nembutal and ketamine/xylazine correspondingly. Functional characteristics (phagocytic activity, oxidative metabolism, CD80/86 and CD206 expression) of phagocytes (microglia, peritoneal macrophages, circulating monocytes and granulocytes) were examined by flow cytometry. Differential leukocyte count was conducted using hematological analyzer. Results. Phagocytes from animals underwent of different protocols of placebo surgery, demonstrated various patterns of functional changes on day 29 after the manipulations. In animals from SO1 group, we observed signs of residual neuroinflammation (pro-inflammatory shift of microglia functional profile) along with ongoing resolution of systemic inflammation (anti-inflammatory metabolic shift of circulating phagocytes and peritoneal macrophages). In rats from SO2 group, pro-inflammatory polarized activation of peritoneal phagocytes was registered along with anti-inflammatory shift in microglia and circulating phagocytes. Conclusions. Sham surgery influences functions of phagocytic cells of different locations even in the far terms after the manipulations. These effects can be considered as combined long-term consequences of surgical brain injury and the use of anesthetics. Our observations evidences, that sham associated non-specific immunomodulatory effects should always be taken into consideration in animal models of inflammatory central nervous system diseases.

show abstract

POLARIZED ACTIVATION OF HUMAN PERIPHERAL BLOOD PHAGOCYTES BY BACTERIOPHAGE–DERIVED DOUBLESTRANDED RNA (LARIFAN) in vitro

Dovhyi

2023

Biotechnol. acta

View full text Add to dashboard Cite

Aim. This study aimed to examine the effect of Larifan on metabolic characteristics of human blood monocytes and granulocytes in vitro. Methods. Four healthy adult men aged 21–26 years were recruited to participate in the study as blood donors. The metabolic profile of human blood monocytes and granulocytes was evaluated by phagocytic activity, reactive oxygen species production, nitric oxide generation, and arginase activity. Phagocytosis of FITC-labeled inactivated Staphylococcus aureus and reactive oxygen species generation were estimated by flow cytometry. Arginase activity was assessed in cell lysates, and nitric oxide generation in supernatants was examined using the Griess reaction. Results. Phagocytic index and reactive oxygen species generation were found to be lower in both human blood monocytes and granulocytes treated with Larifan. The drug caused a dose-dependent increase in nitric oxide production, as well as a decrease in the arginase activity of blood monocytes. Conclusions. Our results indicate the ability of Larifan to reinforce the antiviral properties of resting phagocytes along with containment of oxidative stress development.

show abstract

Effect of Bacteriophage-Derived Double Stranded RNA on Rat Peritoneal Macrophages and Microglia in Normoxia and Hypoxia

Cited by 4 publications

References 39 publications

Pro-inflammatory effects of placebo neurosurgery in rats: age-related features

Pro-inflammatory effects of placebo neurosurgery in rats: age-related features

Long-Term Effects of Sham Surgery on Phagocyte Functions in Rats

POLARIZED ACTIVATION OF HUMAN PERIPHERAL BLOOD PHAGOCYTES BY BACTERIOPHAGE–DERIVED DOUBLESTRANDED RNA (LARIFAN) in vitro

Contact Info

Product

Resources

About