Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

Heparin-enriched plasma proteome is significantly altered in Alzheimer's disease.

INTRODUCTION: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to ß-amyloid (Aß) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches. METHODS: We employed heparin-affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to enrich HBPs from plasma obtained from AD (n = 62) and control (n = 47) samples. These profiles were then correlated to Aß, tau and phosphorylated tau (pTau) CSF biomarkers and plasma pTau181 from the same individuals, as well as a consensus brain proteome network to assess the overlap with AD brain pathophysiology. RESULTS: Heparin enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundant proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude in abundance, were measured across 109 samples. Compared to the consensus AD brain protein co-expression network, we observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, highlighting the complex interplay between the two compartments. Elevated proteins in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate with Aß deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and the APOE4 proteoform. Additionally, heparin-enriched proteins in plasma demonstrated significant correlations with conventional AD CSF biomarkers, including Aß, total tau, pTau, and plasma pTau181. A panel of five plasma proteins classified AD from control individuals with an area under the curve (AUC) of 0.85. When combined with plasma pTau181, the panel significantly improved the classification performance of pTau181 alone, increasing the AUC from 0.93 to 0.98. This suggests that the heparin-enriched plasma proteome captures additional variance in cognitive dementia beyond what is explained by pTau181. CONCLUSION: These findings support the utility of a heparin-affinity approach coupled with TMT-MS for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain.

Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington's disease mice.

BACKGROUND: Therapeutic approaches aimed at lowering toxic mutant huntingtin (mHTT) levels in the brain can reverse disease phenotypes in animal models of Huntington's disease (HD) and are currently being evaluated in clinical trials. Sensitive and dynamic response biomarkers are needed to assess the efficacy of such candidate therapies. Neurofilament light chain (NfL) is a biomarker of neurodegeneration that increases in cerebrospinal fluid (CSF) and blood with progression of HD. However, it remains unknown whether NfL in biofluids could serve as a response biomarker for assessing the efficacy of disease-modifying therapies for HD. METHODS: Longitudinal plasma and cross-sectional CSF samples were collected from the YAC128 transgenic mouse model of HD and wild-type (WT) littermate control mice throughout the natural history of disease. Additionally, biofluids were collected from YAC128 mice following intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting the mutant HTT transgene (HTT ASO), at ages both before and after the onset of disease phenotypes. NfL concentrations in plasma and CSF were quantified using ultrasensitive single-molecule array technology. RESULTS: Plasma and CSF NfL concentrations were significantly elevated in YAC128 compared to WT littermate control mice from 9 months of age. Treatment of YAC128 mice with either 15 or 50 µg HTT ASO resulted in a dose-dependent, allele-selective reduction of mHTT throughout the brain at a 3-month interval, which was sustained with high-dose HTT ASO treatment for up to 6 months. Lowering of brain mHTT prior to the onset of regional brain atrophy and HD-like motor deficits in this model had minimal effect on plasma NfL at either dose, but led to a dose-dependent reduction of CSF NfL. In contrast, initiating mHTT lowering in the brain after the onset of neuropathological and behavioural phenotypes in YAC128 mice resulted in a dose-dependent stabilization of NfL increases in both plasma and CSF. CONCLUSIONS: Our data provide evidence that the response of NfL in biofluids is influenced by the magnitude of mHTT lowering in the brain and the timing of intervention, suggesting that NfL may serve as a promising exploratory response biomarker for HD.

Clarifying the association of CSF Aß, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease.

BACKGROUND: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy. METHODS: This is an observational study, CSF levels of Tau, pTau181, pTau217, Aß38/40/42, sAPPα/ß, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Biomarkers levels were related to the AT(N) framework. (A) and (T) were defined in BALTAZAR with CSF Aß42/40 ratio and pTau217 respectively, and in ADNI with amyloid and tau PET. (N) was defined using total CSF tau in both cohorts. RESULTS: As expected, CSF Aß42 decreased progressively with the AD continuum going from the A-T-N- to the A + T + N + profile. On the other hand, Tau and pTau181 increased progressively with the disease. The final transition from A + T + N- to A + T + N + led to a sharp increase in Aß38, Aß42 and sAPP levels. Synaptic CSF biomarkers BACE1 and neurogranin, were lowest in the initial A + T-N- stage and increased with T + and N + . CSF pTau181 and total tau were closely related in both cohorts. CONCLUSIONS: The early transition to an A + phenotype (A + T-N-) primarily impacts synaptic function. The appearance of T + and then N + is associated with a significant and progressive increase in pathological Alzheimer's disease biomarkers. Our main finding is that CSF pTau181 is an indicator of N + rather than T + , and that N + is associated with elevated levels of BACE1 protein and beta-amyloid peptides. This increase may potentially fuel the amyloid cascade in a positive feedback loop. Overall, our data provide further insights into understanding the interconnected pathological processes of amyloid, tau, and neurodegeneration underlying Alzheimer's disease.

The research trend on neurobrucellosis over the past 30 years (1993-2023): a bibliometric and visualization analysis.

Background: Brucellosis is a zoonotic disease caused by Brucella infection, which is common in pastoral areas. Neurological involvement in brucellosis is relatively rare. But since 1993, continuous studies have been reporting neurological complications of brucellosis, collectively referred to as neurobrucellosis. A bibliometric analysis of existing literature outlines current research progress and gaps and provides guidance for the clinical treatment of neurobrucellosis, promoting patient health in the process of guiding clinical practice, and improving their quality of life. Methods: CiteSpace and VOSviewer are software tools to visualize research trends and networks. By selecting specific areas of interest and configuring the right parameters, the tools can visualize past research data. The study retrieved the literature from the Web of Science Core Collection Database and downloaded it in plain text file format. Citespace6.1.6, VOSviewer v1.6.20, and Microsoft Excel 16.59 were used for analyzing the following terms: countries, institutions, authors' cooperation, journals, keywords, and co-citation. Results: There are eight key results. (1) The publication volume shows a general upward trend. (2) Turkey is the country with the highest publication volume and contributing institutions. (3) Giambartolomei GH, Gul HC, and Namiduru M are the authors with the highest number of publications. (4) Neurology is the journal that published the highest number of related articles (n = 12). (5) "Diagnosis," "meningitis," and "features" are the top three frequently occurring keywords. (6) Keyword clusters show "antibiotic therapy" and "cerebrospinal fluid" have future study value. (7) The burst analysis of the keywords also indicates that "cerebrospinal fluid" may become a prominent keyword in future research. (8) The co-citation analysis concludes three categories of the cited articles, which are diagnosis, therapy, and complications, indicating the past research direction. Conclusion: This study highlights the complexity of neurobrucellosis, presenting the need for advanced diagnostic techniques and multifaceted treatment approaches. While antibiotics remain the cornerstone of therapy, the use of corticosteroids to mitigate inflammatory responses shows promise, albeit with concerns about potential sequelae and relapse. Future research should focus on refining therapeutic strategies that address both the direct effects of infection and the broader immunological impacts to improve patient outcomes and quality of life.

Deep Proteome Analysis of Cerebrospinal Fluid from Pediatric Patients with Central Nervous System Cancer.

The cerebrospinal fluid (CSF) is a key matrix for discovery of biomarkers relevant for prognosis and the development of therapeutic targets in pediatric central nervous system malignancies. However, the wide range of protein concentrations and age-related differences in children makes such discoveries challenging. In addition, pediatric CSF samples are often sparse and first prioritized for clinical purposes. The present work focused on optimizing each step of the proteome analysis workflow to extract the most detailed proteome information possible from the limited CSF resources available for research purposes. The strategy included applying sequential ultracentrifugation to enrich for extracellular vesicles (EV) in addition to analysis of a small volume of raw CSF, which allowed quantification of 1351 proteins (+55% relative to raw CSF) from 400 µL CSF. When including a spectral library, a total of 2103 proteins (+240%) could be quantified. The workflow was optimized for CSF input volume, tryptic digestion method, gradient length, mass spectrometry data acquisition method and database search strategy to quantify as many proteins a possible. The fully optimized workflow included protein aggregation capture (PAC) digestion, paired with data-independent acquisition (DIA, 21 min gradient) and allowed 2989 unique proteins to be quantified from only 400 µL CSF, which is a 340% increase in proteins compared to analysis of a tryptic digest of raw CSF.

Reversible sulcal fluid-attenuated inversion recovery hyperintensity after combined bypass surgery for moyamoya disease - A "crevasse" sign.

Background: Transient fluid-attenuated inversion recovery (FLAIR) hyperintensity is often observed on the operated brain surface after direct or combined bypass surgery for moyamoya disease, but its pathophysiology and clinical significance are still obscure. This study was aimed to clarify the underlying mechanism and clinical significance. Methods: This prospective study included 106 hemispheres of 61 patients with moyamoya disease and analyzed their radiological findings before and after combined bypass surgery. This study also included 11 patients who underwent superficial temporal artery to middle cerebral artery anastomosis for occlusive carotid artery diseases as the controls. Magnetic resonance imaging examination was serially repeated, and cerebral blood flow was measured before and after surgery. Signal intensity ratio (SIR) in the cortical sulci and cortex to the adjacent white matter on FLAIR images was calculated, and the postoperative SIR changes were semi-quantitatively evaluated to assess the temporal profile of postoperative FLAIR hyperintensity. Results: Postoperative FLAIR hyperintensity occurred within the cortical sulci on the operated hemispheres in all moyamoya patients but not in patients with occlusive carotid artery diseases. SIR values started to increase immediately after surgery, peaked at about 4-fold at 4-13 days post-surgery, then declined, and recovered to baseline values over 28 days or later. The magnitude of this phenomenon was proportional to the severity of cerebral ischemia but not to postoperative hyperperfusion. Conclusion: Reversible sulcal FLAIR hyperintensity specifically occurs in the operated hemispheres after direct bypass surgery for moyamoya disease. This "crevasse sign" may represent the mixture of the extensive leakage of oxygen and proteins from the pial arteries into the CSF.

Perspective: Risks/adverse events for epidural spinal injections.

Background: Despite the lack of FDA (Food and Drug Administration) approval, cervical and lumbar epidural spinal injections are frequently performed in the US to address back pain and/or painful radiculopathy. The three major types of injections include; interlaminar/translaminar (ESI), transforaminal (TFESI), or caudal injections. Notably, most studies document little to no clear short-term, and no long-term benefits/efficacy for these injections vs. various placebos. Methods: More adverse events (AE) occurred with cervical© rather than lumbar (L) injections, and more severe AE were attributed to C-TFESI vs. CESI injections. Results: Acute post injection AE symptoms were observed immediately or within 72 post-injection hours. These symptoms included; hypotension, acute respiratory distress, chest pain, upper extremity numbness, weakness, paresthesias, paralysis, and fevers. More AE were attributed to cervical C-TFESI vs. cervical CESI. These AE included; intramedullary/cord injections, intravascular injections (i.e. vertebral artery) resulting in brain stem/cerebellar/cord strokes, epidural abscess/infection, confusion, epidural hematomas, intracranial hypotension, and/or 6th nerve cranial palsies. AE for lumbar LESI/L-TFESI included; infections/abscess, epidural hematomas/subdural hematomas, intravascular injections, cerebrospinal fluid (CSF) leaks/dural tears (DT), and intracranial/postural hypotension. Notably, the vast majority of studies showed little to no short-term, and no long-term benefits for cervical or lumbar ESI/TFESI vs placebos (i.e. mostly consisting of normal saline alone, or saline plus local anesthesia). Conclusion: Epidural cervical and lumbar ESI or TFESI spinal injections demonstrated minimal to no short-term, and no long-term benefits for the treatment of cervical and/or lumbar pain/radiculopathy vs. placebos. Further, more AE were observed for cervical vs. lumbar epidural injections overall, with more AE usually seen with TFESI vs. ESI procedures.

The perivascular space is a conduit for cerebrospinal fluid flow in humans: A proof-of-principle report.

The glymphatic pathway was defined in rodents as a network of perivascular spaces (PVSs) that facilitates organized distribution of cerebrospinal fluid (CSF) into the brain parenchyma. To date, perivascular CSF and cerebral interstitial fluid exchange has not been shown in humans. Using intrathecal gadolinium contrast-enhanced MRI, we show that contrast-enhanced CSF moves through the PVS into the parenchyma, supporting the existence of a glymphatic pathway in humans.

Comparative analysis of meningeal transcriptomes in birds: Potential pathways of resilience to repeated impacts.

The meninges and associated vasculature (MAV) play a crucial role in maintaining cerebral integrity and homeostasis. Recent advances in transcriptomic analysis have illuminated the significance of the MAV in understanding the complex physiological interactions at the interface between the skull and the brain after exposure to mechanical stress. To investigate how physiological responses may confer resilience against repetitive mechanical stress, we performed the first transcriptomic analysis of avian MAV tissues using the Downy Woodpecker (Dryobates pubescens) and Tufted Titmouse (Baeolophus bicolor) as the comparison species. Our findings reveal divergences in gene expression profiles related to immune response, cellular stress management, and protein translation machinery. The male woodpeckers exhibit a tailored immune modulation strategy that potentially dampens neuroinflammation while preserving protective immunity. Overrepresented genes involved in cellular stress responses suggest enhanced mechanisms for mitigating damage and promoting repair. Additionally, the enrichment of translation-associated pathways hints at increased capacity for protein turnover and cellular remodeling vital for recovery. Our study not only fills a critical gap in avian neurobiology but also lays the groundwork for research in comparative neuroprotection.

Population pharmacokinetic modeling of ceftriaxone in cerebrospinal fluid in children: should we be using once- or twice-daily dosing for meningitis?

Guidelines for bacterial meningitis in children recommend intravenous ceftriaxone 50 mg/kg (max 2 g) twice daily (BD) or 100 mg/kg (max 4 g) once daily (OD), leaving the decision regarding the dose frequency to the prescriber. We investigated the cerebrospinal fluid (CSF) penetration of ceftriaxone to evaluate whether one dosing regimen is superior. Unbound ceftriaxone concentrations were measured in serum and CSF samples from children aged 0-18 years treated with ceftriaxone if there was a sample remaining after clinical tests were performed. A serum-CSF population pharmacokinetic model was developed using non-linear mixed-effects modeling. The once- and twice-daily dosing regimens were simulated, and the probability of target attainment (PTA) was determined for maintaining a CSF concentration above a minimum inhibitory concentration (MIC) of 1 mg/L for common meningitis pathogens and 4 mg/L for Staphylococcus aureus for 100% of the dosing interval. Sixteen serum and 87 CSF samples were collected from 98 children (age range 0.1-18.5 years). The final two-compartment serum-CSF model included a renal maturation function with weight scaling on clearance and volume of distribution. The estimated serum:CSF uptake was 20.1%. For MIC 1 mg/L, the 24 h PTA was higher for OD (88%) compared with BD (53%) dosing, although both achieved a 100% PTA at steady state. For S. aureus (MIC 4 mg/L), neither dosing regimen was sufficient. Our findings support the use of a 100 mg/kg once daily regimen for empirical treatment of bacterial meningitis due to earlier achievement of the pharmacodynamic target. Neither dosing regimen was adequate for S. aureus meningitis.

Intrathecal immune reactivity against Measles-, Rubella-, and Varicella Zoster viruses is associated with cerebrospinal fluid inflammation in multiple sclerosis.

BACKGROUND/OBJECTIVES: We aimed to determine in multiple sclerosis (MS) whether intrathecal immunoglobulin G (IgG) production against measles- (M), rubella- (R), and varicella zoster (Z) viruses, which is called MRZ reaction (MRZR) and considered the most specific soluble biomarker for MS, is associated with demographic and basic cerebrospinal fluid (CSF) parameters reflecting inflammation. METHODS: We analyzed the presence of positive MRZR and associations with demographic and clinical routine CSF parameters in 513 patients with MS and 182 non-MS patients. RESULTS: Comparing MS patients versus non-MS patients, positive MRZR (38.8% versus 2.2%; specificity 97.8%; positive likelihood ratio, PLR 17.7) had a better specificity and PLR for MS than CSF-specific OCB (89.5% versus 22.0%; specificity 78.0%; PLR 4.1). A positive MRZR in MS patients was associated with female sex (p = 0.0001), pleocytosis (p < 0.0001), higher frequency of presence of plasma cells in CSF (p = 0.0248), normal CSF/serum albumin ratio (p = 0.0005), and intrathecal production of total IgG or CSF-specific OCB (both p < 0.0001), but not with intrathecal production of total IgA or IgM. CONCLUSIONS: This study confirms the MRZR as a highly specific marker of MS and shows that MRZR-positive MS patients more frequently are female and show inflammatory changes of basic CSF parameters than MRZR-negative MS patients.

Association of preoperative seizures with reduced expression of soluble CD163, an M2 macrophage marker, in the cerebrospinal fluid in isocitrate dehydrogenase wild-type glioblastoma.

PURPOSE: To investigate the relationship between the tumor microenvironment (TME), tumor-related seizures (TRS), and cerebrospinal fluid (CSF) markers that predict preoperative seizures in patients with glioblastoma. METHODS: In total, 47 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma who underwent preoperative CSF examination, 3-T magnetic resonance spectroscopy (MRS), and neurological surgery between January 2017 and December 2023 were included. We measured the concentrations of soluble CD163 (sCD163), a soluble form of the M2 macrophage marker, in the CSF, the metabolite concentration on MRS, and the number of CD163-positive M2 macrophages in the tumor tissue. Factors associated with preoperative seizures were examined. RESULTS: Twelve patients (25.5%) had preoperative seizures. sCD163 levels in the CSF were positively correlated with the number of CD163-positive M2 macrophages in the tumor tissue, and both were significantly lower in the preoperative seizure group than in the non-preoperative seizure group (p = 0.0124 and p < 0.0001, respectively). MRS indicated that only glutathione (GSH) concentrations were higher in the preoperative seizure group than in the non-preoperative seizure group (2.55 mM and 1.87 mM, respectively; p = 0.0171). CD163-positive M2 macrophages were inversely correlated with GSH levels. sCD163 in the CSF had a high predictive accuracy (sensitivity, 91.7%; specificity, 54.3%; and area under the receiver operator curve, 0.745) for preoperative seizures. CONCLUSIONS: The CSF level of sCD163 is useful for predicting the TME and preoperative seizures in IDH wild-type glioblastoma.

Tandem mass spectrometry-based assay for heparan-N-sulphatase in paediatric CSF: A potential pharmacodynamic biomarker for mucopolysaccharidosis type IIIA therapy.

Mucopolysaccharidosis type IIIA is a lysosomal storage disorder caused by mutations in the gene coding for heparan-N-sulphatase, a crucial enzyme in the degradation of heparan sulfate. In mucopolysaccharidosis type IIIA, heparan sulfate accumulates in the lysosomes, predominantly affecting the central nervous system. It is the most common and most severe form of mucopolysaccharidosis type III, with onset typically before the age of ten years. There is an ongoing effort to develop therapies that aim at restoring enzyme function in the brain. This study introduces a novel tandem mass spectrometry method for assessing heparan-N-sulphatase activity in pediatric cerebrospinal fluid from healthy and disease individuals. Analysis of cerebrospinal fluid samples revealed marked differences in enzyme activity, with mucopolysaccharidosis type IIIA individuals exhibiting significantly reduced levels. This new method could serve as a valuable tool for evaluating the efficacy of future therapeutic interventions targeting sulphatase activity restoration in the brain.

CSF complement proteins are elevated in prodromal to moderate Alzheimer's disease patients and are not altered by the anti-tau antibody semorinemab.

INTRODUCTION: Growing evidence suggests a role for neuroinflammation in Alzheimer's disease (AD). We investigated complement pathway activity in AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti-tau antibody semorinemab. METHODS: Immunoassays were applied to measure CSF complement proteins C4, factor B (FB), C3 and their cleavage fragments C4a, C3a, and factor Bb (Bb) in AD patients and a separate cognitively unimpaired (CU) cohort. RESULTS: All measured CSF complement proteins were increased in AD versus CU subjects, with C4a displaying the most robust increase. Finally, semorinemab did not have a significant pharmacodynamic effect on CSF complement proteins. DISCUSSION: Elevated levels of CSF C4a, C4, C3a, C3, Bb, and FB are consistent with complement activation in AD brains. Despite showing a reduction in CSF soluble tau species, semorinemab did not impact complement protein levels or activity. Further studies are needed to determine the value of complement proteins as neuroinflammation biomarkers in AD. HIGHLIGHTS: Cerebrospinal fluid (CSF) complement proteins C4a, C3a, Bb, C4, C3, and factor B levels were increased in Alzheimer's disease (AD) patients compared to a separate cognitively unimpaired (CU) cohort. Baseline CSF complement protein levels were correlated with neuro-axonal degeneration and glial activation biomarkers in AD patients. The investigational anti-tau antibody semorinemab did not impact CSF complement protein levels or activity relative to the placebo arm.

Calcified Hofmann's ligaments as the cause of spinal cerebrospinal fluid leaks associated with spinal ventral dural tears.

OBJECTIVE: Patients with spinal CSF leaks often have ventral dural abnormalities (type 1 CSF leaks); however, the pathological mechanism for developing dural abnormalities is unknown. The authors investigated whether calcified dural ligaments contribute to the development of ventral dural tears, which cause spinal CSF leaks. METHODS: Consecutive patients diagnosed with type 1 CSF leaks who had spiculated spinal lesions between 2010 and 2024 were included. Clinical, radiological, surgical, and histological findings were reviewed. RESULTS: Nineteen patients with type 1 CSF fistulas had spiculated spinal lesions (15 men; median age 47 years, range 28-71 years). Spiculated lesions showed a high density on CT, and the median lesion length was 3.5 mm (range 1.6-9.1 mm). Spiculated lesions were consistently located at the center of the ventral dural abnormalities, penetrated the dura mater, and were located in the high thoracic spine (T1-5) in 13 patients (68%) and in the low thoracic spine (T8-12) in 6 (32%). These spinal lesions were connected to the posterior longitudinal ligament, but not to the vertebral body or disc. Histologically, they did not include degenerative osteophytic or discogenic tissues, mostly comprised fibrotic tissues with some calcification, and were consistent with calcified dural ligaments. CONCLUSIONS: The anatomical characteristics of spiculated spinal lesions associated with ventral dural abnormalities are consistent with those of calcified dural ligaments, referred to as Hofmann's ligaments. These ligaments are important for neurosurgeons, neurologists, and neuroradiologists who diagnose and treat type 1 CSF fistulas.

GLP-1 programs the neurovascular landscape.

Readily available nutrient-rich foods exploit our inherent drive to overconsume, creating an environment of overnutrition. This transformative setting has led to persistent health issues, such as obesity and metabolic syndrome. The development of glucagon-like peptide-1 receptor (GLP-1R) agonists reveals our ability to pharmacologically manage weight and address metabolic conditions. Obesity is directly linked to chronic low-grade inflammation, connecting our metabolic environment to neurodegenerative diseases. GLP-1R agonism in curbing obesity, achieved by impacting appetite and addressing associated metabolic defects, is revealing additional benefits extending beyond weight loss. Whether GLP-1R agonism directly impacts brain health or does so indirectly through improved metabolic health remains to be elucidated. In exploring the intricate connection between obesity and neurological conditions, recent literature suggests that GLP-1R agonism may have the capacity to shape the neurovascular landscape. Thus, GLP-1R agonism emerges as a promising strategy for addressing the complex interplay between metabolic health and cognitive well-being.

Acute bacterial meningitis without cerebrospinal fluid pleocytosis in children: results from a nationwide prospective surveillance system between 2001 and 2022.

OBJECTIVES: We aimed to describe cases of acute bacterial meningitis (ABM) without cerebrospinal fluid (CSF) pleocytosis and clinical and biological characteristics of children. METHODS: We analyzed results of a nation-wide population-based prospective surveillance study of acute ABM in children aged 3 months to 15 years in France. Absence of CSF pleocytosis was defined as CSF leukocyte count ≤5/mm. RESULTS WE INCLUDED: 4,754 cases of acute ABM from 2001 to 2022: 173 patients (3.6%) did not have CSF pleocytosis. ABM cases without CSF pleocytosis were mainly related to meningococcus (70% vs 44% with CSF pleocytosis, p<0.001). When performed in CSF with normal leukocyte count, Gram staining was positive for 33%, culture for 80%, PCR results for 41%, and antigen detection for 20% of cases. Case fatality rate was higher for cases without than with CSF pleocytosis (18% vs 6%, p<0.001). On multivariate analysis, absence of CSF pleocytosis was only associated with seizures before hospital arrival (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.6, p<0.01). CONCLUSIONS: ABM without CSF pleocytosis is infrequent but not exceptional, particularly in children with seizures before hospital arrival. Extended vaccination against meningococcus could prevent this clinical form with a high case fatality rate.

Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system.

The widespread use of plastics has led to increased micro- and nanoplastics (MNPs) pollution, resulting in significant environmental challenges and concerns about potential harm to human health. This study investigated whether certain types of MNPs can accumulate in the human central nervous system (CNS) and trigger inflammatory responses, particularly after CNS infection. Our analysis of 28 cerebrospinal fluid (CSF) samples from 28 patients with or without CNS infection revealed that only polystyrene (PS), polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) were capable of selectively entering the human CNS. Concentrations of PP and PE were positively correlated with the CSF albumin index. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly increased in patients with CNS infections. However, concentrations of MNPs were not significantly associated with CSF levels of IL-6 or IL-8. Overall, these findings suggest that specific MNPs can penetrate the human CNS, especially after impairment of the blood-brain barrier. Notably, MNPs derived from commonly used plastics did not significantly induce or exacerbate inflammation in the human CNS.

Identifying idiopathic intracranial hypertension in a hospital-based chronic headache population: Utility of magnetic resonance imaging, magnetic resonance venography and trans-orbital sonography.

BACKGROUND: One of the most underestimated types of chronic headaches is headaches as a result of cerebro-spinal fluid dysregulation disorders. Idiopathic intracranial hypertension (IIH) presents with headache and visual symptoms and usually is associated with papilledema. We identified patients with IIH in a chronic headache population presenting to a hospital-based headache clinic, and studied its associations with clinical, sonographic and magnetic resonance imaging (MRI) findings. METHODS: Of 168 patients, 141 chronic headache patients were identified and completed the study procedures (semi-structured medical interview, fundus examination, MRI brain with magnetic resonance venography (MRV) and trans-orbital sonography (TOS)). Patients with abnormal findings underwent lumbar puncture for opening pressure. RESULTS: The prevalence of IIH was 27%. IIH patients were of higher age, had gnawing/throbbing headache in the vertex in most cases, and had higher body mass index. Fundus examination had a sensitivity of 79% and a specificity of 98% for the detection of IIH cases. Approximately 23% of IIH patients had no papilledema. The most sensitive MR sign was found to be transverse sinus stenosis. TOS showed optic nerve sheath dilation in 35.7% of IIH without papilledema cases. CONCLUSIONS: The prevalence of IIH is high in the chronic headache population and should be suspected in the headache clinic setting, particularly because there is significant overlap with migraine symptomatology. MRI/MR venography and TOS can be useful adjunct tests to identify IIH patients.