Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4‐deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti‐inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R.

Mechanisms of the brain‐related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle‐aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin‐positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ‐carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety‐like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety‐like behavior in rats with CP/CPPS comparing to their sham‐operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety‐like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons.

Pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear since it represents an interplay between immunological, endocrine, and neuropsychiatric factors. Patients suffering from CP/CPPS often develop mental health-related disorders such as anxiety, depression, or cognitive impairment. The aim of this study was to investigate depression-like behavior, learning, and memory processes in a rat model of CP/CPPS and to determine the alterations in hippocampal structure and function. Adult male Wistar albino rats ( in each group) from CP/CPPS (single intraprostatic injection of 3% λ-carrageenan, day 0) and Sham (0.9% NaCl) groups were subjected to pain threshold test (days 2, 3, and 7), depression-like behavior, and learning-memory tests (both on day 7). Decreased pain threshold in the scrotal region and histopathological presence of necrosis and inflammatory infiltrate in prostatic tissue confirmed the development of CP/CPPS. The forced swimming test revealed the depression-like behavior evident through increased floating time, while the modified elevated plus maze test revealed learning and memory impairment through prolonged transfer latency in the CP/CPPS group in comparison with Sham ( and , respectively). Biochemical analysis showed decreased serum levels of testosterone in CP/CPPS group vs. the Sham ( ). The CP/CPPS induced a significant upregulation of ICAM-1 in rat cortex ( ) and thalamus ( ) and increased GFAP expression in the hippocampal astrocytes ( ) vs. Sham, suggesting subsequent neuroinflammation and astrocytosis. Moreover, a significantly decreased number of DCX+ and Ki67+ neurons in the hippocampus was observed in the CP/CPPS group ( ) vs. Sham, indicating decreased neurogenesis and neuronal proliferation. Taken together, our data indicates that CP/CPPS induces depression-like behavior and cognitive declines that are at least partly mediated by neuroinflammation and decreased neurogenesis accompanied by astrocyte activation.

Sleep architecture alterations, among which sleep fragmentation is highly prevalent, represent risk factors for a variety of diseases, ranging from cardiovascular to brain disorders, including anxiety. What mediates anxiety occurrence upon sleep fragmentation is still a matter of debate. We hypothesized that the sleep fragmentation effects on anxiety are dependent on its duration and mediated by increased oxidative stress and alterations in the number of parvalbumin (PV+) interneurons in the hippocampus. Sleep was fragmented in rats by the treadmill method during a period of 14 days (SF group). Rats with undisturbed sleep in the treadmill (TC group) and those receiving equal amounts of treadmill belt motion (EC group) served as controls. To assess anxiety, we subjected rats to the open field, elevated plus maze, and light‐dark tests on the 0, 7^th, and 14^th day. Upon the last test, brain structures were sampled for oxidative stress assessment and PV+ interneuron immunohistochemistry. The results of ethological tests of anxiety‐linked behavior suggested duration‐dependent anxiogenic potential of sleep fragmentation. Rats’ anxiety‐linked behavior upon sleep fragmentation significantly correlated with oxidative stress. The rats with fragmented sleep (SF) showed significantly higher oxidative stress in the hippocampus, thalamus, and cortex, compared to controls (TC and EC), while the antioxidant enzymes’ activity was significantly decreased. No significant differences were observed in hippocampal PV+ interneurons among these groups. Our results showed that duration of sleep fragmentation is a significant determinant of anxiety‐linked behavior, and these effects are mediated through oxidative distress in the brain. Herein, it is revealed that the sleep fragmentation‐oxidative stress‐anxiety axis contributes to our better understanding of pathophysiological processes, occurring due to disrupted sleep patterns.

The Institute of Histology and Embryology "Prof. dr Aleksandar Đ. Kostić" is celebrating its 100th anniversary this year. The founder of the Institute, the first Professor of Histology and Embryology, and the first Director of the Institute was Professor Aleksandar Đ. Kostić, PhD, one of the last Renaissance figures of the XX century. Investing tremendous effort and enthusiasm he developed the Institute, from a bare room, with only four walls, a floor, and a ceiling, into a building which was, in the late 1920s, considered to be one of the most modern buildings housing a scientific institute in South-East Europe, which, for that time, had exceptionally good conditions for research and teaching, a very dedicated staff, but also a highly developed research potential, a rich library, terminology unit, and a photography department. After the bombing of Belgrade and of the Institute, on April 6, 1941, he rebuilt the building and reestablished the Institute, yet once more, during his lifetime, and then, due to ideological differences, he was forced into retirement and removed from the Faculty. He was morally rehabilitated posthumously, together with a group of teachers from the Faculty of Medicine, at the session of the Academic Council of the Faculty of Medicine held on January 24, 2001.