Introduction

The NLRP3 inflammasome plays a significant role in the pathogenesis of obesity by contributing to the development of chronic low-grade inflammation, systemic inflammation, and, consequently, neuroinflammation.

Quercetin is a flavonoid which possesses anti-inflammatory properties, therefore representing a potential modulator of neuroinflammatory process, metabolic regulators such as the fat mass obesity-associated gene (Fto) and TNF-α/NF-κB/NLRP3 Inflammasome pathway genes.

Studies in animal models have shown that quercetin exerts a wide range of effects over inflammatory processes, suggesting potential therapeutical applications. Fto is a well-known gene associated with obesity risk, body mass index, energy homeostasis and hypothalamic control of appetite and satiety. Altered Fto expression influences metabolic and inflammatory responses and plays a relevant role in inflammatory-related diseases.

We hypothesized that quercetin inhibits overexpression of Fto and the activation of the TNF-α/NF-κB/NLRP3 Inflammasome pathway in the hypothalamus of high-fat-diet Wistar rats.

Objectives

To evaluate mRNA expression of Fto and components of the TNF-α/NF-κB/NLRP3 inflammasome pathway in the hypothalamus of high-fat diet-fed Wistar rats by quantitative PCR (qPCR).

Methodology

After 2 weeks of acclimation, three groups of Wistar rats (200 ± 20 g) were randomly assigned to three groups (n = 6 each group): (a) standard diet (SD), (b) high-fat diet (HD), and (c) high-fat diet with quercetin (HD+Q). Quercetin was administered intragastrically at a dose of 50 mg/kg/day for 12 weeks.

At the end of the intervention period, rats were euthanized and the hypothalamus was collected. Total RNA was isolated using the TriZol method, purified with isopropanol and 75% ethanol, quantified, and its purity verified by nanodrop 2000 spectrophotometer.

cDNA was synthetized from 100 ng of total RNA using random primers. The mRNA expressions of Fto, Tnf, Tnfrs1a, Tradd, Ripk1, Map3k7, Ikbkb, Ikbkg, Nek7, Nfkbia, Nlrp3, Pycard, Casp1, Il1b and Il18 through qPCR. Β-Actin were used as housekeeping genes.

Results

The HD+Q group showed a significant decrease in the mRNA expression of Fto and pro-inflammatory genes involved in the TNF-α/NF-κB/NLRP3 inflammasome pathway compared with the HD group. In contrast, the HD group showed a significant increase in the expression of these genes relative to the SD group.

Conclusions

Quercetin downregulates mRNA expression of Fto and key components of the TNF-α/NF-κB/NLRP3 inflammasome pathway in the hypothalamus of high-fat-diet-fed Wistar rats. These findings suggest that quercetin may represent a promising therapeutic candidate for targeting obesity-associated neuroinflammation.

Introduction: Carbon tetrachloride (CCl₄), is industrial solvent, hose living close to textile and chemical factories are exposed to CCl₄ and are at great risk. The toxic effect of CCl₄ is believed to be due to trichloromethyl radicals (CCl₃^•) which causes extensive membrane molecular and mitochondrial damages, and ultimately cell death by necrosis and ammonia toxicity. Many common medications cause hepatotoxicity and neurotoxic chemicals including ethanol also cause OS in the brain.

Aim: The aim of this present study was to determine whether administration of α-lipoic acid, a potent iron-chelating antioxidant ergogenic aid could decrease CCl₄-induced hepatotoxicity and neurotoxicity.

Materials & Methods: Male albino rats (4-months old, 250 gm body wt) were pretreated with α-lipoic acid (Started 3-days prior to CCl₄ administration) (ALA:100mg/Kg b.wt, orally via an oral cannula for 11 days), followed by oral ingestion with the CCl₄ (CCl₄ in Olive oil, 1.6 mL/kg b.wt). At the end of the 11-days, the animals were sacrificed and biological samples were collected for the estimation of biomarkers of liver dysfunction, biomarkers of OS and inflammation in the brain.

Results: Application of α-lipoic acid mitigated the toxic onslaught of CCl₄-induced-toxicity and exerted hepatoprotective effects by significantly (p<0.001) reducing SGOT, SGPT, ﻻ-GT, bilirubin, MDA, 8- OHdG, IL-6, TNF-α, XO, NOS, NADPH-oxidase and augmentation of serum total protein, A/G ratio. Further, ALA protects the liver and brain by increasing antioxidants such as GSH, SOD, Catalase, GST, GPx, GR, G6PD, spares ATP, DNA and modulation of PARP-1.

Conclusion: Knowledge of the epigenetic and molecular mechanisms involved in the CCl₄-induced hepatotoxicity in this model is the key to identifying potential therapeutic targets for liver dysfunction associated with a variety of hepatic disorders including alcoholic cirrhosis and brain dysfunction due to ammonia toxicity.

Introduction: Postherpetic neuralgia (PHN) is the most frequent chronic complication of herpes zoster and is characterized by persistent neuropathic pain caused by sensory nerve injury and neuroinflammatory responses. Although clinical risk factors are well documented, the genetic architecture underlying PHN susceptibility remains poorly defined. Genome-wide association studies (GWASs) represent a powerful tool to identify common variants that may contribute to neuronal vulnerability, persistent inflammation, or dysregulated pain signaling.

Methods: We performed a secondary analysis of publicly available summary statistics from the GWAS Catalog (GCST012124), derived from a genome-wide association study conducted in individuals with PHN. The dataset included all reported SNP-level associations for the trait MONDO_0041052. Variants were evaluated based on reported effect allele, beta coefficients, p-values, genomic context, and nearest-gene annotation. Biological interpretation was performed through gene-function review and known pathways implicated in neuropathic pain.

Results: Five genome-wide significant or near-significant loci were identified. The strongest associations were rs4773840 mapped to KIF1B (β = 0.18, p = 3.8×10⁻⁸) and rs10982356 near PTPRZ1 (β = 0.17, p = 7.6×10⁻⁸), both genes involved in axonal transport, neuronal signaling, and glial modulation. Additional variants included rs9655009 within PRKCE (p = 4×10⁻⁷), a key kinase in nociceptive sensitization, rs10887816 near CXCR4, implicated in neuroinflammation, and rs17057519 in a regulatory non-coding region (WDR11-AS1). These loci converge on pathways relevant to neuronal injury, synaptic modulation, and chronic pain maintenance.

Conclusions: This GWAS highlights candidate genetic factors that may increase susceptibility to PHN by altering axonal integrity, inflammatory responses, and pain-signaling pathways. The findings support a multifactorial neurobiological basis for PHN and provide mechanistic targets for future translational and therapeutic research.

Introduction: Valproic acid (VPA) is a broad-spectrum anticonvulsant that is particularly effective against epilepsy, acting by increasing GABA (cerebral inhibitor) activity and blocking sodium channels. Despite its therapeutic benefits, VPA presents significant risks. Objective: This study aimed to evaluate the neurotoxic effects of VPA in Wistar rats. Methods: Forty-eight male and female Wistar rats were divided into six groups: (1 and 4) a control group, (2 and 5) a VPA 200 mg/kg group, and (3 and 6) a VPA 400 mg/kg group. The products were administered daily by gavage for 60 days. Wistar rats weighing between 100 and 300 g exposed to VPA and their offspring constituted our study population. Daily observations were made for three generations of Wistar rats. Behavioral, biochemical, cerebral histological, and reproductive parameters were evaluated, as well as 8-OH-dG dosage by PCR on one genetic region. Results: Observations revealed significant alterations across three generations. Wistar rats exposed to VPA exhibited brain alterations, reproductive dysfunction, and alopecia. In the second and third generations, our results showed brain atrophy, limb abnormalities, tumors, spina bifida, and histological alterations. Our results highlighted a significant decrease in biochemical parameters, stress, memory impairment, neurodevelopmental disorders, and reproductive system dysfunction. Conclusion: The abnormalities observed in the three generations of Wistar rats during our study reflect VPA-induced neurotoxicity at the doses studied after the exposure of the first generation. Our future work will consist of consolidating a neurotoxicity model based on APV.

Introduction: Neuroinflammation is the main factor of secondary brain injury following traumatic brain injury (TBI). At the same time, neural cells are most sensitive to damaging factors. The effectiveness of therapeutic approaches to treat neuroinflammation is limited. This study aims to identify new strategies for regulating neuroinflammation in TBI.

Methods: The effect of experimental therapy with sympatholytic reserpine on the expression of M1 and M2 microglial markers (Iba1, iNOS, CD206), the mature neuron marker (NeuN), and the expression of the apoptotic marker Caspase-3 by neurons and microglia in the motor cortex and subventricular zone (SVZ) of ICR mice with TBI was studied using the immunohistochemical method.

Results: Reserpine reduced the number of Iba1⁺ microglia, including polarized M1 microglia, and Caspase-3⁺ microglia in the motor cortex and SVZ of mice with TBI. Reserpine also reduced the number of polarized M2 microglia in the SVZ. However, experimental therapy did not affect the content of NeuN⁺ cells, including NeuN⁺Caspase-3⁺ cells, in the motor cortex and SVZ of mice with TBI.

Conclusion: Sympatholytic reserpine may be a promising compound for developing a new approach to combating neuroinflammation in TBI. We believe that additional administration of drugs that stimulate the differentiation of neural progenitor cells may promote nerve cell regeneration.

Centella asiatica (CA), a well known Ayurvedic medicine, enriched with bioflavonoids is believed to have beneficial effects in improving learning and memory in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinsonism, multiple sclerosis and senile dementia. It also exerts a potent antioxidant-iron chelating and neuroprotective effects and enhances cognition in a variety of clinical condditions. Acute ischemia (AI) followed by reperfusion is known to bring about a major biochemical and behavioral alterations. In the present study the effect of Centella asiatica extract (CAE) on acute cerebral reperfusion (ACR) and long-term cerebral hypoperfusion (LTCH) in aged rats (Body wt 300g, 28-month old). was investigated. Transient brain ischemia (TBI) was induced under anaesthesia by clamping bilateral common carotid arteries (BCCAO) for 30 min and then reperfusion was allowed for 60 mins. The biomarkers of oxidative stress like malondialdehyde (MDA), superoxide dismutase (SOD), proinflammatory cytokines (PICKs), DNA content, 8-OHdG, nitric oxide synthase (NOS), poly(ADP-ribose polymerase)-1 and relevant biomarkers and behavioral and biochemical studies were estimated. In the present investigation, acute ischemia-reperfusion (AI-R) induced increases all the biomarkers of oxidative stress, PICKs, oxidative DNA-damage, DNA- repair enzymes such as NOS, PARP-1. CAE pre-administration (300 mg/kg body wt, p.o. for 7 days, CAE administration started 3-days prior to occlusion) ameliorated the reperfusion induced biochemical alterations in aged rats. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness accompanied by deficits in learning and memory confirmed by related tests). Further, CAE treatment (200 mg/kg body wt, p.o. for 1 month) alleviated these behavioral, cognitive and biochemical alterations significantly. The results suggest that CAE enriched with bioflavonoids and tritripenoids may be useful in cerebrovascular insufficiency conditions associated with normal aging, hypertension and brain stroke.

Introduction. Aging impairs the multisensory integration and cognitive control essential for posture regulation. Declining cerebellum–prefrontal cortex coordination disrupts attentional shifting, working memory, and executive flexibility, weakening balance responses, slowing adaptation, and increasing instability. The stabilometric target test on a force platform assesses cognitive–motor interaction by analyzing attentional load and sensorimotor updating during posture control. This study aimed to characterize age-related changes in cognitive–motor integration and evaluate whether athletic training mitigates cortical decline and optimizes sensorimotor–cognitive function.

Methods. Forty-four participants were divided by age (≤45 years, n = 24, median 36.5 years; >45 years, n = 20, median 55.5 years) and athletic experience (nonexperienced, n = 24; experienced, n = 20). All performed a stabilometric target test on the Stabilan-01-2 platform (OKB Ritm, Taganrog, Russia) on firm and soft surfaces, with stabilogram recording and frequency analysis. Statistical significance (p < 0.05, q < 0.1) was assessed using Student’s t-test or the Mann–Whitney U test with FDR-BH correction. Athletic experience effects were analyzed via regression, adjusting for age, sex, and training.

Results. Age and athletic experience significantly explained the variation in stabilographic data (p < 0.05 and p < 0.01, respectively) on a firm surface. Age was negatively associated with stability parameters (r < 0), while athletic experience showed positive associations (r > 0) during the stabilometric target test engaging attention and postural control. On a soft surface, no intergroup differences were observed, as support deprivation triggers adaptive mechanisms that maintain posture regardless of athletic training level. Regression analysis revealed that athletic experience was significantly associated with increased stability in both age groups.

Conclusion. Athletic experience enhanced stabilometric performance, improving visual–postural control and compensating for age-related decline. These results suggest stabilometric improvements are linked to training cognitive mechanisms, particularly attention and spatial orientation.

Neuroinflammation plays a crucial role in the development and progression of variousneurodegenerative diseases. Therapeutic strategies aimed at protecting physiological
functions of brain endothelial cells are being explored as potential treatments for these
conditions. It is necessary to have experimental models that accurately represent the effects
of neuroinflammation, as existing models are often not sufficiently representative of human
physiology and the specific challenges of central nervous system diseases with a vascular
pathology. Considering the need for a more accurate simulation strategy of the selective
properties and limitations of the blood–brain barrier (BBB), we established a BBB-on-a-chip
model, which consists of a co-culture of human stem cell-based brain endothelial cells and
brain pericytes, to study how BBB permeability is altered under pathological conditions and
to discover protective compounds to counteract BBB injury. Our preliminary results showed
that the thrombin–fibrinogen interaction-based hydrogel self-assembled model holds great
potential for use in preclinical studies, as it was possible to mimic BBB properties in vitro.
Brain endothelial cells formed an established vascular network visualized by PECAM
staining along with a positive signal for ɑ-smooth muscle actin for pericytes. Modeling BBB
injury with pro-inflammatory cytokines to promote neuroinflammation was successful with a
lower calcein AM signal and higher positivity for propidium iodide. This setup will be used to
test novel ways to improve BBB functions under neuroinflammation. In the future we aim to
identify and optimize new therapeutic compounds before testing them on animal or human
models.

Introduction

Bistable perception occurs when stimuli present ambiguous sensory information that can be interpreted in two different ways, spontaneously changing in aware experience, and is widely used as an experimental approach in consciousness research. In the present study, we compared the neural activity induced by dynamic bistable stimuli that create illusory directional flips with that of rotating patterns changing direction.

Methods

Stimuli were spiral glass patterns of similar appearance. Six of them included a sequence of 1,000 different patterns, while the other six contained patterns rotating either clockwise or counterclockwise, changing direction unpredictably.

Thirty-six subjects participated in this study and had to press a joystick button whenever they perceived a change in the stimulus motion direction.

EEG was recorded at 26 positions. Epochs taken 1,000 msec before button presses were classified in two categories: illusory and real rotation directional flips. Representational similarity analysis (RSA) was applied using Pearson correlation. We examined the overall similarity within and across categories, its time course, and its spatiotemporal distribution (searchlight analysis).

Results

No significant differences in the overall neuronal similarity and its time course were found within or across categories, although real rotations showed the highest correlation. Category-specific information appeared earlier for illusory reversals than for real directional flips.

The searchlight analysis indicated differences in average correlation among brain regions and time windows for both types of directional flips’ categories. Illusory flips induce lower similarity of neural activity but involved more brain regions than the real flips. Both types of flips displayed significant neural similarity across all electrodes approximately 250 milliseconds before the button press.

Conclusions

Directional transitions in bistable stimuli elicit neural activity that resembles real directional changes. However, illusory reversals recruit more widespread cortical regions and show distinct temporal dynamics, consistent with evidence that bistable perception engages distributed brain networks.

Despite growing evidence linking diabetes to brain dysfunction, the specific long-term effects of type 1 (T1D) and type 2 diabetes (T2D) on hippocampal and prefrontal cortex (PFC) function remain poorly characterized. This study aimed to provide a comprehensive comparison of the chronic neurobiological, cognitive, and behavioral consequences of sustained hyperglycemia in experimental models of T1D and T2D. By integrating behavioral assessments with biochemical and neurochemical analyses, we sought to delineate diabetes type-specific patterns of dysfunction within the hippocampus and PFC. Adult rats were randomly divided into three groups: Sham, T1D, and T2D. T1D was induced by a single intraperitoneal injection of streptozotocin (STZ), while T2D was established via nicotinamide (NA) administration 15 minutes prior to STZ injection. Behavioral and cognitive assessments were conducted during the final phase of the 100-day experimental period. Following testing, blood samples were collected for biochemical analyses, and the hippocampus and PFC were dissected to assess oxidative stress markers, inflammatory mediators, acetylcholinesterase (AChE) activity, BDNF levels, and Na⁺/K⁺-ATPase activity. Histological examinations using Nissl staining were performed to evaluate neuronal integrity. After 100 days of hyperglycemia, both diabetic models exhibited significant functional and structural alterations in the hippocampus and PFC. T2D was associated with pronounced oxidative stress and inflammation, correlating with anxiety- and depression-like behaviors (P < 0.05). Conversely, T1D rats displayed more extensive cognitive impairment, along with severe neurochemical and structural disruptions, including marked BDNF depletion, significant Na⁺/K⁺-ATPase reduction, and elevated AChE activity (P < 0.05), indicative of greater neuronal stress and degeneration. These findings underscore diabetic encephalopathy as a multifactorial disorder involving interrelated deficits in neurotrophic support, metabolic regulation, and neurotransmitter balance. While T2D is characterized predominantly by oxidative and inflammatory stress, T1D exerts more profound neurochemical and structural damage within the hippocampus and prefrontal cortex.