LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS

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 n...

Full description

Bibliographic Details
Main Authors: Zh. Oliynyk, M. Rudyk, Kalachniuk, T. Dovbynchuk, G.Tolstanova, Skivka
Format: Article
Language:English
Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 2022-04-01
Series:Biotechnologia Acta
Subjects:
Online Access:http://biotechnology.kiev.ua/images/2_2022/oliynyk_2_2022.pdf
_version_ 1797756827802271744
author Zh. Oliynyk
M. Rudyk
Kalachniuk
T. Dovbynchuk
G.Tolstanova
Skivka
author_facet Zh. Oliynyk
M. Rudyk
Kalachniuk
T. Dovbynchuk
G.Tolstanova
Skivka
author_sort Zh. Oliynyk
collection DOAJ
description 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.
first_indexed 2024-03-12T18:07:14Z
format Article
id doaj.art-32d3b3e72f194e7990ac53b01d781d71
institution Directory Open Access Journal
issn 2410-7751
2410-776X
language English
last_indexed 2024-03-12T18:07:14Z
publishDate 2022-04-01
publisher National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
record_format Article
series Biotechnologia Acta
spelling doaj.art-32d3b3e72f194e7990ac53b01d781d712023-08-02T09:27:35ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryBiotechnologia Acta2410-77512410-776X2022-04-01152374610.15407/biotech15.02.037LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATSZh. Oliynyk0M. Rudyk1Kalachniuk2T. Dovbynchuk3G.Tolstanova4Skivka5Taras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”, UkraineTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”, UkraineNational University of Life and Environmental Sciences of Ukraine,Department of biochemistry and Physiology of Animals, KyivTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”, UkraineTaras Shevchenko National University of Kyiv, Educational and Scientific Institute of High Technologies, UkraineTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”, UkraineAnimal 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.http://biotechnology.kiev.ua/images/2_2022/oliynyk_2_2022.pdfsham surgeryphagocytesneuroinflammationsystemic inflammation
spellingShingle Zh. Oliynyk
M. Rudyk
Kalachniuk
T. Dovbynchuk
G.Tolstanova
Skivka
LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
Biotechnologia Acta
sham surgery
phagocytes
neuroinflammation
systemic inflammation
title LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
title_full LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
title_fullStr LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
title_full_unstemmed LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
title_short LONG-TERM EFFECTS OF SHAM SURGERY ON PHAGOCYTE FUNCTIONS IN RATS
title_sort long term effects of sham surgery on phagocyte functions in rats
topic sham surgery
phagocytes
neuroinflammation
systemic inflammation
url http://biotechnology.kiev.ua/images/2_2022/oliynyk_2_2022.pdf
work_keys_str_mv AT zholiynyk longtermeffectsofshamsurgeryonphagocytefunctionsinrats
AT mrudyk longtermeffectsofshamsurgeryonphagocytefunctionsinrats
AT kalachniuk longtermeffectsofshamsurgeryonphagocytefunctionsinrats
AT tdovbynchuk longtermeffectsofshamsurgeryonphagocytefunctionsinrats
AT gtolstanova longtermeffectsofshamsurgeryonphagocytefunctionsinrats
AT skivka longtermeffectsofshamsurgeryonphagocytefunctionsinrats