Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits.

The aim of our study was to investigate the effects of binge drinking on prooxidant/antioxidant system in rat liver in acute cadmium (Cd) intoxication. In experiment male Wistar rats were used and divided into following groups: 1. control, 2. ethanol-treated group, in five subsequent doses of 2 g/kg administered by orogastric tube, 3. Cd-treated group in a single dose of 2.5 mg/kg intraperitoneally, 4. group that received Cd 12 hours after the last dose of ethanol. Blood and liver samples were collected for determination of oxidative stress parameters, 24 hours after treatment. When administered in combination, ethanol and Cd induced a more pronounced increase in serum and liver malondialdehyde level than either of these substances alone (p<0.01). Liver manganese superoxide dismutase (MnSOD) activity was increased both in ethanol and Cd-treated group (p<0.01), while liver copper/zinc superoxide dismutase (Cu/ZnSOD) activity was elevated in Cd group only. However, when administered in combination, ethanol and Cd induced a more pronounced decrease in liver MnSOD and Cu/ZnSOD activity 24 hours after treatment (p<0.01). Based on our study, it can be concluded that ethanol may act sinergistically with Cd in inducing lipid peroxidation and reduction in liver SOD activity.

Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A_2AR/A₁R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A_2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A_2AR on glial cells is observed. Finally, increased glial A₁R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.

COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

Background: The study aimed to assess antioxidative status using standard biochemical analyses in multiple sclerosis patients during relapse and remission. Also, to evaluate the effects of gender, drug-modified treatment and clinical characteristics of multiple sclerosis on analyzed antioxidants. Methods: The study consisted of 178 relapse-remitting multiple sclerosis patients (61 relapse/117 remission), 93 females and 85 males, with a mean age of 40.9±9.8 (average age of 40.9) and 80 matched healthy controls. Ongoing drug-modified treatment received 132 patients. The serum levels of uric acid, total bilirubin, albumin, and transferrin were analyzed in both patients and controls. Extended Disability Status Scale (EDSS), disease duration and annual relapse rate were used as clinical characteristics of multiple sclerosis. Results: The antioxidant status was decreased in multiple sclerosis patients compared to controls. There was no statistically significant difference in antioxidant levels between relapse and remission. Women had less favourable antioxidative defence than men, with lower uric acid, total bilirubin and albumin. Negative correlations were found between disease duration, uric acid, annual relapse rate and total bilirubin. The use of disease-modifying therapy increased albumin levels. Conclusion: The use of standard biochemical analyses as an antioxidant tool in patients with multiple sclerosis was evidenced in this study. The gender and clinical characteristics affected antioxidant status, highlighting the need for personalized complementary adds to antioxidative therapy in multiple sclerosis.