Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)-and lipopolysaccharide (LPS)-induced models of Parkinson's disease (PD). Experiments were carried out on adult male Wistar rats: 1 -intact animals; 2 -sham-operated animals and 3 -6-OHDAand LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and shamoperated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology.

The astrogliosis was considered as a beneficial process to protect neurons and repair the tissue after CNS insult for a long time. However, numerous study indicate that under some specific conditions, reactive astrocytes can exacerbate neuroinflammation and tissue damage. Parkinson's disease (PD) is one of the most common neurodegenerative diseases that is a major medical and social problem. The progressive course of the disease requires continuous therapy, in the later stages it causes a disability of the patient, which entails the need for constant care and causes significant economic losses. The pathophysiological bases of CP remain unclear, making it impossible to diagnose the disease early, predict its course, and develop pathogenetic treatments. Neuroinflammation of polyetiological genesis, whose development involves micro- and astroglial cells, is considered to be a leading pathogenetic factor of CP. However, the functional state of astroglia in the conditions of development of this neuropathology remains the least studied. The aim of the study was to investigate the functional state of astroglia in rats with PD induced by bacterial lipopolysaccharide (LPS-PD). It has been established that the development of LPS-PD in rats is accompanied by reactive astrogliosis with overexpression of glial fibrillar acidic protein (GFAP) and products of its degradation by astrocytes of the hippocampal region of the brain. Overexpression of GFAP is associated with an increase in the level of myelin basic protein (MBP) in brain homogenates and a decrease in the level of neuronal NO synthase.

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.