High altitude cerebral edema (HACE), a fatal terminal stage of acute mountain sickness (AMS), is triggered by rapid exposure to hypoxia at high altitudes. The pathophysiology of HACE is complex, involving multiple key processes including energy metabolism disorders, oxidative stress, blood-brain barrier (BBB) injury, and neuroinflammation, all of which interact to drive disease progression. Lactylation, a novel epigenetic regulatory mechanism discovered in 2019, provides a fresh perspective for HACE research.

This study integrates the latest research findings on the pathophysiology of HACE, lactate metabolism, and the role of lactylation in hypoxia-related diseases (such as cancer and ischemic-hypoxic diseases). It focuses on analyzing the potential molecular mechanisms of lactylation in HACE, including its regulation of the HIF-1α/NF-κB axis, inflammation, and metabolism, and discusses existing lactylation regulation strategies.

In HACE, hypoxia-driven glycolysis elevates lactate, promoting protein lactylation (e.g., NuRD complex in microglia, which is correlated with proinflammatory cytokines). Lactylation may regulate HIF-1α/NF-κB axis, inflammation, and metabolism in HACE pathogenesis. Currently, methods such as the inhibition of lactate dehydrogenase (LDH) /monocarboxylate transporters and the use of histone deacetylase inhibitors have been proven effective in regulating lactylation.

Lactylation is a key link connecting metabolic disorders and neuroinflammation in HACE. However, the dual role of lactate in neuroprotection and neuroinjury under hypoxic conditions still requires further exploration. Future research should focus on deciphering the molecular networks related to HACE and developing precise intervention strategies to provide new directions for HACE treatment.

Ocrelizumab (OCR) and rituximab (RTX) are anti-CD20 monoclonal antibodies (CD20Mabs) used in the treatment of relapsing multiple sclerosis (RMS). While both are effective at reducing relapses and new MRI lesions in clinical trials, real-world data on discontinuation rates and reasons for stopping therapy are limited.

This observational retrospective chart review included patients from two MS clinics in British Columbia, Canada. RMS patients treated with at least one infusion of OCR or RTX between January 2017 and March 2023 were included. Primary outcomes were reasons for discontinuation and discontinuation rates, with a secondary outcome of time to discontinuation.

In total, 881 RMS patients were included, with 478 on OCR and 403 on RTX. A total of 16.9% of patients on OCR and 14.9% on RTX discontinued therapy over 1643 and 694 patient-years, respectively (p = 0.46). Reasons for discontinuation included: side effects (33.3%), insurance coverage (17.0%) and clinical or radiological disease activity (11.3%). Discontinuation rates at 12, 24 and 36 months were 3.5%, 8.2% and 12.5% for OCR, and 6.4%, 14.8% and 22.2% for RTX, respectively (p = 0.0089). Median time to discontinuation was 21 months on OCR and 11.5 months on RTX (p < 0.0001). On Cox regression analysis, treatment with RTX was the only variable associated with discontinuation (hazard ratio 1.72, 95% CI 1.20–2.45).

Discontinuation rates of CD20Mabs were low, and the most common reason for stopping was side effects. Although not designed for comparison, our study suggests RMS patients may persist longer on OCR than RTX.

Autoimmune psychosis (AP) and other autoimmune psychiatric syndromes (APS) are associated with central nervous system antibodies. This study investigated related magnetic resonance spectroscopic imaging (MRSI) signatures and their correlations with electroencephalography (EEG), cerebrospinal fluid (CSF), and psychometric/neuropsychological measures.

Twenty-eight adults with suspected antibody-positive AP spectrum syndromes were compared with 28 matched healthy controls. Inclusion in the patient group was based on the APS concept, resulting in a heterogeneous group with uniform autoimmunity. MRSI was performed using a spiral-encoded Mescher-Garwood localised adiabatic selective refocusing 3D-MRSI sequence. Glutamate+glutamine (Glx), gamma-aminobutyric acid (GABA), total N-acetylaspartate (tNAA), and total creatine (tCr) were reported as ratios to tNAA and/or tCr. EEG was analysed for intermittent rhythmic delta/theta activity (IRDA/IRTA) using independent component analysis.

No significant differences in Glx, GABA, tNAA, or tCr ratios were observed between patients and controls. Correlation analyses in patients showed a trend for a negative association of the IRDA/IRTA rate before hyperventilation with the GABA/tCr ratio in both hippocampi and with the GABA/tNAA ratio in the left hippocampus and Glx/tCr ratio in the right putamen and pallidum. Significant positive correlations were observed between inflammatory CSF markers (white blood cell count and IgG Index) and GABA/tCr and GABA/tNAA ratios in the left caudate nucleus and right isthmus cingulate and thalamus, as well as between negative symptoms in PANSS and higher GABA/tCr ratios in the right putamen.

No group differences were identified; however, correlations suggest a link between neuroinflammatory CSF markers and negative symptoms with GABAergic signalling in patients. Multimodal diagnostic approaches may provide a better understanding of the link between neuroinflammation, neurochemistry, and EEG slowing.

Perimenopausal women often experience physiological and psychological decline due to the effects of oestrogen fluctuations and the decline of ovarian function, leading to significantly increased depression rates, decreases in the quality of life and mental health issues. Studies have shown that the gut microbiota exerts anti-perimenopausal depression (PMD) effects via the microbiota-gut-brain (MGB) axis, the mechanisms of which may be related to inflammation. In this review, we discuss the effects and mechanisms of gut microbiota in PMD and provide new insights for future PMD treatment.

This review elaborates on the role of MGB axis in PMD from different aspects of inflammation, including gut microbiota metabolites, inflammatory signaling pathways, and clinical applications.

Disorders of gut microbiota and decreased levels of gut microbiota metabolites (short-chain fatty acids, monoamine neurotransmitters) may cause PMD. The mechanism of intestinal microbiota-mediated inflammation may be related to TLR4/NF-κB pathway, NOD-like receptor protein 3 (NLRP3) inflammasome pathway and JAK-STAT pathway. At the same time, it was found that gut microbiota (probiotics, prebiotics, etc.) had good therapeutic potential in the treatment of PMD.

MGB axis mediated inflammation may play an important role in PMD. The application of gut microbiota in the treatment of PMD patients has profound clinical transformation value, but a lot of efforts are still needed.

MicroRNAs (miRNAs) alterations in patients with bipolar disorder (BD) are pivotal to the disease’s pathogenesis. Since obtaining brain tissue is challenging, most research has shifted to analyzing miRNAs in peripheral blood. One innovative solution is sequencing miRNAs in plasma extracellular vesicles (EVs), particularly those neural-derived EVs emanating from the brain.

We isolated plasma neural-derived EVs from 85 patients with BD and 39 healthy controls (HC) using biotinylated antibodies targeting a neural tissue marker, followed by miRNA sequencing and expression analysis. Furthermore, we conducted bioinformatic analyses and functional experiments to delve deeper into the underlying pathological mechanisms of BD.

Out of the 2,656 neural-derived miRNAs in EVs identified, 14 were differentially expressed between BD patients and HC. Moreover, the target genes of miR-143-3p displayed distinct expression patterns in the prefrontal cortex of BD patients versus HC, as sourced from the PsychENCODE database. The functional experiments demonstrated that the abnormal expression of miR-143-3p promoted the proliferation and activation of microglia and upregulated the expression of proinflammatory factors, including IL-1β, IL-6, and NLRP3. Through weighted gene co-expression network analysis, a module linking to the clinical symptoms of BD patients was discerned. Enrichment analyses unveiled these miRNAs’ role in modulating the axon guidance, the Ras signaling pathway, and ErbB signaling pathway.

Our findings provide the first evidence of dysregulated plasma miRNAs within neural-derived EVs in BD patients and suggest that neural-derived EVs might be involved in the pathophysiology of BD through related biological pathways, such as neurogenesis and neuroinflammation.

Alcohol use disorder (AUD) is a major global health concern associated with limited treatment efficacy and high relapse rates. Recent research highlights the gut microbiota as a critical modulator of AUD pathophysiology through its influence on the gut–brain axis. Chronic alcohol consumption induces gut dysbiosis, characterised by reduced microbial diversity, impaired gut barrier function and systemic inflammation, which perpetuate neuroinflammation, stress dysregulation and neurotransmitter imbalances. These disruptions exacerbate addiction-related behaviours, contributing to the cycle of dependence and relapse. This critical review synthesises current evidence on the role of gut microbiota in AUD, examining the mechanisms linking dysbiosis to addiction and evaluating therapeutic interventions such as probiotics, prebiotics, faecal microbiota transplantation (FMT), psychobiotics and dietary modifications.

The strategies evaluated show significant potential in restoring microbial homeostasis and improving AUD outcomes, but challenges remain, including gaps in mechanistic understanding, variability in methodologies, and barriers to clinical translation.

There is a need for multi-omics research, personalised medicine approaches and integrated treatment models to advance microbiota-based therapies. Gut microbiota-targeted strategies might then transform AUD management, offering innovative and personalised solutions for addiction recovery.

Late-life depression (LLD) arises from a complex interplay among biological, psychological, and social factors. Biologically, three main hypotheses have been proposed to explain the distinct clinical features of LLD. The vascular hypothesis supports vascular-related white matter changes in the development of LLD, while the neurodegenerative hypothesis suggests that LLD might be a prodrome of neurodegenerative diseases. The inflammatory hypothesis, which is the main focus of this review, posits that heightened inflammation underlies LLD directly or indirectly through neurodegenerative and microvascular alterations.

This is a non-systematic review on the role played by inflammation in the pathophysiology of LLD and the related opportunities to define biomarkers and therapeutic targets. We searched PubMed from January 2010 through March 2025 for relevant English-language studies.

Patients with LLD have elevated circulating levels of inflammatory biomarkers (e.g., C-reactive protein and interleukin-6) as well as evidence of neuroinflammation. Although the exact origin of this inflammatory profile remains unclear, it is thought to be exacerbated by immune cell senescence and the presence of physical comorbidities, including cardiovascular and metabolic diseases. Pharmacological (e.g., selective serotonin receptor inhibitors) and non-pharmacological (e.g., diet, physical interventions) approaches for LLD seem to exert their therapeutic effect, at least in part, through inflammation-related mechanisms.

Recognizing the unique features of LLD compared to depression in other periods of life is an important step toward its proper management. More specifically, understanding the role of inflammation in LLD holds both theoretical and practical implications, including anti-inflammatory or immune-based strategies as potential therapeutic interventions.

Previous studies on the aetiology of attention-deficit/hyperactivity disorder (ADHD) emphasise high heritability and the influence of maternal smoking during pregnancy, highlighting the role of gene–environment interactions. Additionally, low-grade peripheral inflammation is frequently observed in individuals with ADHD. However, the underlying neurobiological mechanisms remain unclear. We aimed to investigate neuroinflammatory signalling contributing to ADHD and explore behavioural and molecular changes in a mouse model.

We examined neuroinflammatory signalling using a perinatal nicotine exposure (PNE) model via immunohistochemistry combined with cortical thickness (CT) measurement in the subregions of the prefrontal cortex (PFC). Mice were exposed to nicotine via drinking water containing 300 μg/ml nicotine and 2% sucrose starting 2 weeks before mating until weaning to induce ADHD-like symptoms, as opposed to controls receiving drinking water containing 2% sucrose alone. Behavioural tests were conducted to assess ADHD-like behaviours and accompanying anxiety on postnatal week 5. Inflammatory pathways in the anterior cingulate cortex (ACC), prelimbic cortex (PL), and infralimbic cortex (IL) were examined using Iba-1 and NF-κB immunolabelling, and microglial morphology was analyzed.

Findings showed increased CT, microglial cell number, activity, and NF-κB activation in the ACC, which correlated with attention-related impairment in PNE mice. Increased Iba-1 levels in the PL and IL, along with elevated NF-κB activation in the IL, were observed in PNE mice, which corresponded with a significant increase in anxiety-like behaviours compared to controls. PNE mice also morphologically exhibited microglia activation in all three subregions.

PNE contributes to ADHD development through neuroinflammatory signalling, a common end pathway.

Cognitive function plays a pivotal role in assessing an individual’s quality of life. This research aimed to investigate how azelaic acid (AzA), a natural dicarboxylic acid with antioxidant and anti-inflammatory properties, affects aluminium chloride (AlCl3)-induced behavioural changes and biochemical alterations in the hippocampus of rats.

Thirty-two male Wistar rats divided into four groups received distilled water, AzA 50 mg/kg, AlCl3 100 mg/kg and AzA plus AlCl3, respectively, by oral gavage for 6 weeks. Behavioural changes were evaluated using open-field maze, elevated plus maze, novel object recognition (NOR), passive avoidance task, and Morris water maze (MWM) tests. Also, malondialdehyde (MDA), carbonyl protein, tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-kappa B (NF-κB), C/EBP homologous protein (CHOP), glycogen synthase kinase-3 beta (GSK-3β), brain-derived neurotrophic factor (BDNF) and acetylcholinesterase (AChE) activity were examined.

AzA significantly affected AlCl3-provoked anxiety-like behaviours and learning and memory impairments. It also reduced the toxic effect of AlCl3 on MDA, carbonyl protein, TNF-α, IL-1β, NF-κB and GSK-3β status; however, its beneficial effects on AlCl3-induced changes of CHOP, BDNF and AChE activity were not significant.

These findings disclosed that AzA could improve behavioural and cognitive function and almost limit the oxidative stress and neuroinflammation caused by AlCl3.

Inflammation is increasingly recognised as a fundamental component of the pathophysiology of major depressive disorder (MDD), with a variety of inflammatory biomarkers playing pivotal roles. These markers are closely linked to both the severity of symptoms and the responsiveness to treatments in MDD.

This scoping review aims to explore the scientific literature investigating the complex relationships between inflammatory biomarkers and depression, by identifying new studies and critical issues in current research.

Following the PRISMA Extension for Scoping Reviews guidelines, we systematically searched databases including PubMed, Scopus, PsycINFO, Open Grey and Cochrane Library. Our search focused on articles published from 1 January 2020 to 1 May 2024. We included studies evaluating inflammatory biomarkers in adult patients with MDD, utilising observational and randomised controlled trial designs, and review studies.

Our analysis examined 44 studies on the complex interplay between inflammation and its multiple effects on MDD. Significant associations between specific inflammatory biomarkers and depression severity were found, requiring cautious interpretation. We also highlight several methodological limitations in the current studies, which warrant caution in directly applying these findings to clinical practice. However, identified methodologies show potential for using these biomarkers as diagnostic tools or therapeutic targets, including anti-inflammatory interventions.

The findings emphasise the need for sophisticated, integrative research to understand inflammation's role in MDD. Future studies should identify specific biomarker panels for diagnosing depression and bridging peripheral biomarker measurements with central neuroinflammatory processes, leading to better diagnostic and treatment strategies.

To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.

Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioural paradigms to evaluate non-motor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.

6-OHDA-lesioned rats exhibited memory impairments and despair-like behaviour in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. CBD decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behaviour that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favoured the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.

The present findings suggest a potential beneficial effect of CBD on non-motor symptoms induced by intra-nigral 6-OHDA infusion in rats.