Evidence shows that Autism Spectrum Disorder (ASD) stems from an interplay of genetic and environmental factors, which may include propionic acid (PPA), a microbial byproduct and food preservative. We previously reported that in vitro treatment of neural stem cells with PPA leads to gliosis and neuroinflammation. In this study, mice were exposed ad libitum to a PPA-rich diet for four weeks before mating. The same diet was maintained through pregnancy and administered to the offspring after weaning. The brains of the offspring were studied at 1 and 5 months postpartum. Glial fibrillary acidic protein (astrocytic marker) was significantly increased (1.53 ± 0.56-fold at 1 M and 1.63 ± 0.49-fold at 5 M) in the PPA group brains. Tubulin IIIβ (neuronal marker) was significantly decreased in the 5 M group. IL-6 and TNF-α expression were increased in the brain of the PPA group (IL-6: 2.48 ± 1.25-fold at 5 M; TNF-α: 2.84 ± 1.16-fold at 1 M and 2.64 ± 1.42-fold, at 5 M), while IL-10 was decreased. GPR41 and p-Akt were increased, while PTEN (p-Akt inhibitor) was decreased in the PPA group. The data support the role of a PPA-rich diet in glia over-proliferation and neuro-inflammation mediated by the GPR41 receptor and PTEN/Akt pathway. These findings strongly support our earlier study on the role of PPA in ASD.

OBJECTIVE: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the destruction of the myelin sheath within the central nervous system. The etiology of MS involves a complex interplay of genetic, environmental, and immunological factors. Recent studies indicated the potential role of the choroid plexus (CP) in the pathogenesis and progression of MS. This systematic review aims to assess existing research on the volume alterations of the CP in MS patients compared to the normal population.
METHODS: A comprehensive search was conducted across databases including PubMed, Embase, Scopus, and Web of Science up to June 2024. Data from the included studies were synthesized using a meta-analytical approach with a random-effects model, assessing heterogeneity with the I2 and Tau-squared indices.
RESULTS: We included 17 studies in this systematic review. The meta-analysis, which included data from eight studies reporting CP volume relative to TIV, found a statistically significant increase in CP volume in MS patients compared to healthy controls (HCs). The SMD was 0.77 (95% CI: 0.61 to 0.93), indicating a large effect size. This analysis showed no heterogeneity (I² = 0%). A separate meta-analysis was conducted using five studies that reported CP volume as normalized volume, resulting in an SMD of 0.63 (95% CI: 0.2-1.06).
CONCLUSIONS: This study demonstrates an increase in CP volume among MS patients compared to HCs, implying the potential involvement of CP in MS pathogenesis and/or progression. These results show that CP might serve as a radiological indicator in the diagnosis and prognosis of MS.

Traumatic Brain Injury (TBI) is attributed to a forceful impact on the brain caused by sharp, penetrating bodies, like bullets and any sharp object. Some popular instances like falls, traffic accidents, physical assaults, and athletic injuries frequently cause TBI. TBI is the primary cause of both mortality and disability among young children and adults. Several individuals experience psychiatric problems, including cognitive dysfunction, depression, post-traumatic stress disorder, and anxiety, after primary injury. Behavioral changes post TBI include cognitive deficits and emotional instability (anxiety, depression, and post-traumatic stress disorder). These alterations are linked to neuroinflammatory processes. On the other hand, the direct impact mitigates inflammation insult by the release of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF-α, exacerbating neuronal injury and contributing to neurodegeneration. During the excitotoxic phase, activation of glutamate subunits like NMDA enhances the influx of Ca2+ and leads to mitochondrial metabolic impairment and calpain-mediated cytoskeletal disassembly. TBI pathological insult is also linked to transcriptional response suppression Nrf-2, which plays a critical role against TBI-induced oxidative stress. Activation of NRF-2 enhances the expression of anti-oxidant enzymes, providing neuroprotection. A possible explanation for the elevated levels of NO is that the stimulation of NMDA receptors by glutamate leads to the influx of calcium in the postsynaptic region, activating NOS\'s constitutive isoforms.

BACKGROUND: Status Epilepticus (SE) stands as a prominent neurological emergency, showing a mortality rate of approximately 20%. Since February 2021, a worldwide vaccination campaign has been launched against the Coronavirus 19 disease (COVID-19) pandemic. Several possible vaccine-related adverse events have been identified, including neurological manifestations. SE is beginning to surface in literature as an emergent condition in COVID-19-vaccinated individuals, though defined reasons accounting for this correlation are still missing.
METHODS: We report two cases of SE related to the SARS-CoV-2 vaccine. In addition, we performed a systematic search of the literature to identify the consistency of the association between the SARS-CoV-2 vaccine and the SE onset. The following databases were consulted: PubMed and Google Scholar.
RESULTS: Two novel super-refractory status epilepticus (SRSE) cases associated with the BNT162b2 mRNA COVID-19 vaccine were identified. Both patients received the second dose of the vaccine about 14 days prior to SE onset. Patients showed a non-convulsive semiology and were treated with a combined anesthetic and immunomodulant therapy, leading to SE resolution in both cases. The literature review identified seven additional cases, primarily non-convulsive SE. Four patients received the Spikevax (ex-COVID-19 Moderna mRNA -1273 vaccine), 2 patients the BNT162b2 (Pfizer/Biotech), and 1 patient the ChAdOx1-s (AstraZeneca) vaccine. The first vaccine dose (5/7, 71.4%) emerged as the most frequently associated with SE onset, which manifested at an average of 4.5 days (± 3.4) following vaccination. Five patients presented RSE and required continuous intravenous anesthetic drug administration. Resolution of SE was achieved in all cases.
CONCLUSIONS: Status Epilepticus is a rare complication associated with Sars-CoV-2 vaccines. Additional studies are needed to ascertain the potential association between Sars-CoV-2 vaccines and status epilepticus.

Accumulation of the pro-inflammatory protein S100A9 has been implicated in neuroinflammatory cascades in neurodegenerative diseases (NDs) such as Alzheimer\'s disease (AD) and Parkinson\'s disease (PD). S100A9 co-aggregates with other proteins such as α-synuclein in PD and Aβ in AD, contributing to amyloid plaque formation and neurotoxicity. The amyloidogenic nature of this protein and its role in chronic neuroinflammation suggest that it may play a key role in the pathophysiology of these diseases. Research into molecules targeting S100A9 could be a potential therapeutic strategy to prevent its amyloidogenic self-assembly and to attenuate the neuroinflammatory response in affected brain tissue. This work suggests that bioactive natural molecules, such as those found in the Mediterranean diet, may have the potential to alleviate neuroinflammation associated with the accumulation of proteins such as S100A9 in neurodegenerative diseases. A major component of extra virgin olive oil (EVOO), hydroxytyrosol (HT), with its ability to interact with and modulate S100A9 amyloid self-assembly and expression, offers a compelling approach for the development of novel and effective interventions for the prevention and treatment of ND. The findings highlight the importance of exploring natural compounds, such as HT, as potential therapeutic options for these complex and challenging neurological conditions.

UNASSIGNED: Depression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood.
UNASSIGNED: We examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program.
UNASSIGNED: We found that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1.
UNASSIGNED: Our findings reveal a protective link between the Prevotella-dominant microbiome and depression, associated with a less inflammatory environment and moderated symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, highlight potential avenues for microbiome-targeted therapies in depression management.

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It has been shown that many miRNAs, including miR-193b-3p, are differentially expressed in Parkinson\'s disease (PD). Dysregulation of miR-193b-3p/PGC-1α axis may alter homeostasis in cells and can induce an inflammatory response commonly accompanied by metabolic disturbances. The aim of the present study is to investigate if dysregulation of the miR-193-3p/PGC-1α axis may contribute to the pathological changes observed in the PD brain. Brain tissue were obtained from middle frontal gyrus of non-demented controls and individuals with a PD diagnosis. RT-qPCR was used to determine the expression of miR-193b-3p and in situ hybridization (ISH) and immunological analysis were employed to establish the cellular distribution of miR-193b-3p. Functional assays were performed using SH-SY5Y cells, including transfection and knock-down of miR-193b-3p. We found significantly lower expression of miR-193b-3p in the early stages of PD (PD4) which increased throughout disease progression. Furthermore, altered expression of PGC-1α suggested a direct inhibitory effect of miR-193b-3p in the brain of individuals with PD. Moreover, we observed changes in expression of insulin after transfection of SH-SY5Y cells with miR-193b-3p, which led to dysregulation in the expression of several pro- or anti - inflammatory genes. Our findings indicate that the miR-193b-3p/PGC-1α axis is involved in the regulation of insulin signaling. This regulation is crucial, since insulin induced inflammatory response may serve as a protective mechanism during acute situations but potentially evolve into a pathological process in chronic conditions. This novel regulatory mechanism may represent an interesting therapeutic target with potential benefits for various neurodegenerative diseases.

BACKGROUND: Traumatic brain injury (TBI), especially neuroinflammation after TBI persists for a long time and causes significant neurodegenerative pathologies and neuropsychiatric problems.
OBJECTIVE: In this study, the neuroprotective effect of AnGong NiuHuang (AGNH) on TBI was investigated and the mechanism was revealed by integrating multiple omics.
METHODS: The rats with TBI were administrated with AGNH for 5 consecutive days and the effect was evaluated by using modified neurologic severity score (mNSS), brain edema, H&E staining, Nissl staining and TUNEL staining. The mechanism was revealed by using RNA sequencing (RNA-seq) and metabolomic analysis. The inflammatory factors, apoptosis-related proteins and identified vital targets were validated by enzyme-linked immunosorbent assay, western blotting and immunofluorescence staining.
RESULTS: Administration of AGNH decreased mNSS, brain edema, brain structure damage, but increased Nissl body density in the rats with TBI. Additionally, AGNH reduced IL-1β, IL-17A, TNF-α, MMP9, MCP-1, IL-6, Bax and TUNEL staining,but elevated Bcl2 level. Integrating transcriptomic analysis and metabolomic analysis identified vital targets and critical metabolic pathways. Importantly, AGNH treatment reduced the expression of TLR4, MYD88, NLRP3, BTK, IL-18 and Caspase 1 as well as glycerophospholipid metabolism-related protein AGPAT2 and PLA2G2D, and decreased the nuclear translocation of NF-κB p65 in the brain of TBI rats. Additionally, AGNH increased phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylethanolamine (PE), but decreased 1-acyl-sn-glycero-3-phosphocholine (LysoPC) in the metabolic pathway of glycerophospholipid metabolism.
CONCLUSIONS: Taken together, AGNH inhibited NF-κB/NLRP3 axis to suppress neuroinflammation, cell apoptosis and pyroptosis, and improved metabolic pathways of glycerophospholipid metabolism after TBI.

BACKGROUND: Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further investigation.
OBJECTIVE: The study investigated the pathogenesis of PQ-induced neuroinflammation of the substantia nigra pars compacta (SNPC) and cerebellum and evaluated the potential effect of selenium nanoparticles (SeN) against such neurotoxicity.
METHODS: Thirty-six mice were randomly divided into three groups; Control group, PQ group: mice received PQ 10 mg/kg (i.p), and PQ + SeN group; mice received PQ in addition to oral SeN 0.1 mg/kg. All regimens were administered for 14 days. The mice\'s brains were processed for biochemical, molecular, histological, and immune-histochemical assessment.
RESULTS: SeN increased the SNPC and cerebellum antioxidants (reduced glutathione, glutathione peroxidase, and superoxide dismutase 1) while decreasing malondialdehyde concentration. Also, SeN increased the anti-inflammatory interleukin (IL)-10 and decreased the pro-inflammatory IL-1β and -6 along with improving the angiogenic nitric oxide and reducing caspase-1. Further, western blots of phosphorylated Janus kinase (JAK2)/signal transducer and activator of transcription3 (STAT3) proteins showed a significant decline. Those improving effects of SeN on SNPC, and cerebellum were supported by the significantly preserved dopaminergic and Purkinje neurons, the enhanced myelin fibers on Luxol fast blue staining, and the marked increase in Olig-2, Platelet-derived growth factor-alpha, and tyrosine hydroxylase immunoreactivity.
CONCLUSIONS: SeN could mitigate PQ-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.