Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

COVID-19-associated encephalopathy: connection between neuroinflammation and microbiota-gut-brain axis.

While neurological complications of COVID-19, such as encephalopathy, are relatively rare, their potential significant impact on long-term morbidity is substantial, especially given the large number of infected patients. Two proposed hypotheses for the pathogenesis of this condition are hypoxia and the uncontrolled release of proinflammatory cytokines. The gut microbiota plays an important role in regulating immune homeostasis and overall gut health, including its effects on brain health through various pathways collectively termed the gut-brain axis. Recent studies have shown that COVID-19 patients exhibit gut dysbiosis, but how this dysbiosis can affect inflammation in the central nervous system (CNS) remains unclear. In this context, we discuss how dysbiosis could contribute to neuroinflammation and provide recent data on the features of neuroinflammation in COVID-19 patients.

THE NEUROLOGICAL MANIFESTATIONS AND FUNCTIONAL INDEPENDENCE IN PATIENTS WITH ENCEPHALOPATHIES OF DIFFERENT TYPES.

OBJECTIVE: Aim: To access the neurological manifestations and activities of daily living in patients with encephalopathy of one of the following types: post-infectious, chronic traumatic encephalopathy, alcohol-induced, and microvascular ischemic disease of the brain. PATIENTS AND METHODS: Materials and Methods: In the period of 2021-2022 we examined 520 patients, who signed the informed consent, taking into account their age, sex, occupation, the cause, and the disease duration. Such parameters were evaluated, as the data of neurological manifestations, the activities of daily living (Barthel index), cognitive functioning (MoCA-test), and statistical methods (Statistica 13.0). RESULTS: Results: A probable influence of the age factor on the frequency of occurrence of different types of encephalopathies was established (χ2=235.05; p<0.001). The cognitive impairment was diagnosed in 53.79 % of patients with CTE, 66.21% with SVD, and 58.82% with AE. 40% of patients with CTE are dependent on their activities of daily living, among patients with SVD - 31,72 %, among patients with AE - 44.12%, among patients with PIE - 53.91%. 17.97% of patients with PIE had moderate dependence by the Barthel index. Thus, the severity of disability doesn't depend on the age or sex of patients but is correlating with the duration of the disease. CONCLUSION: Conclusions: The neurological manifestations in patients with encephalopathies and their activities of daily living were studied profoundly and the data obtained opened new directions in the following research.

POLYMORPHISM OF ACE AND AT2R1 GENES AS A GENETIC BACKGROUND FOR DIFFERENT TYPES OF ENCEPHALOPATHIES.

OBJECTIVE: The aim: To study the prevalence of ACE I/D and AT2R1 A1166C gene polymorphisms in patients with CTE, SVD, AIE, and PIE and to assess the influence of the presence of a particular genotype of the studied genes on the occurrence and/or progression of encephalopathies. PATIENTS AND METHODS: Materials and methods: A total of 96 patients with encephalopathies of various genesis (chronic traumatic encephalopathy (CTE) n=26; chronic alcohol-induced encephalopathy (AIE) n=26; microvascular ischemic disease of the brain (or cerebral small vessel disease, (SVD)) n=18; post-infectious encephalopathy (PIE) n=26) were involved in the study. The molecular genetic study was performed in the molecular genetics laboratory of the State Institution «Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine¼, Kyiv. Statistical processing of the results was performed using the STATISTICA 10.0 program. RESULTS: Results: In patients with various types of encephalopathies, probable changes in the frequency distribution of genotypes of polymorphic variants I/D of the ACE gene were established (11.11% vs. 33.33% - carriers of the I/I genotype, 27.78% vs. 50.00% - carriers of the I/D genotype and 61.11% vs. 16.67% - carriers of the D/D genotype) and A1166C of the AT2R1 gene (22.22% vs. 66.67% - carriers of the A/A genotype, 50.00% vs. 25.00% - carriers A/C genotype, 27.78% versus 8.33% - carriers of the C/C genotype) compared to individuals of the control group only in patients with SVD. The presence of the D allele and the D/D genotype of the ACE gene is associated with a statistically significant increase in the risk of SVD development and progression (respectively, 4.2 times (95% CI (1.39-12.72)) and 7.9 (95% CI ( 1.31-47.05)) times). A similar trend was established for the carrier of the C allele of the A1166C polymorphic variant of the AT2R1 gene in patients with SVD: a 4.3-fold increase in the risk of development and progression (95% CI (1.30-13.86). In addition, there is a probable dependence between carrier genotype A/C of the AT2R1 gene and increased risk of PIE and AIE by 4.8 and 5.7 times, respectively. CONCLUSION: Conclusions: Therefore, results suggest the reasonability to include the I/D of the ACE gene polymorphism investigation in the genetic panel of encephalopathies.

The comprehensive evaluation of patients' condition in recovery and residual periods of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The aim: is to evaluate peculiarities of clinical and neurological characteristics, quality of life, brain morphometry changes and metabolic deviations of patients, who suffered from aneurysmal subarachnoid hemorrhage. PATIENTS AND METHODS: Materials and methods: In the period of 2016-2019 we examined 114 patients, who signed the informed consent, taking into account their age, clinical and anatomical form of hemorrhage, disease duration, Hunt-Hess severity grade, complications of acute period. Such parameters were evaluated, as clinical and neurological characteristics, the degree of the Barthel index and the modified Rankin scale, cognitive functioning (MoCA), psycho-emotional sphere and quality of life (HADS, SF-36), morphometric parameters based on brain computed tomography measurements, explored the indicators of apoptosis, mitochondrial dysfunction, intracellular oxidative stress. RESULTS: Results: Сephalgia (90,35 %), pyramidal syndrome (53,50 %), sensibility deficit (36,84 %) were leading among the all neurological syndromes. Slight dependence and disability grade was found during assessment of the Barthel index and the modified Rankin scale. In 85,96 % of patiens we revealed cognitive impairment of different severity grades. The anxiety was manifested in 65,79 %, depression - in 64,91 % of patients. Due to the morphometry data, the process of cerebral atrophy was detected (central - in 26,31 % of patients, cortical - in 16,67% and mixed - in 28,07 %). AnV+ and PI+ - cells level exceeded normal values in 2,88 and 1,96 times while the level of JC-1+ and ROS+-cells - in 2,17 and 2,82 times (p<0,01). CONCLUSION: Conclusions: Having studied clinical and neurological, neuropsychological, morphometric and metabolic factors, we found their pathogenetic role in the course of late recovery and residual periods of aneurysmal subarachnoid hemorrhage, that would help us to improve the diagnostic tactics and reveal the predictors of unfavorable outcome.