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BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.e., brain atrophy, and retinal layer thinning). METHODS: We designed an observational prospective mono-center study in RRMS patients initiating ALZ treatment. Patients were assessed at baseline (month 0) and thereafter annually for five years with clinical measures, synthetic magnetic resonance imaging (SyMRI) and optical coherence tomography (OCT), with a re-baseline SyMRI scan and an OCT exam 24 months after initiating ALZ. Persons with neurological symptoms but without evidence of neurological disease served as symptomatic controls (SCs, n = 27). RESULTS: Forty-nine RRMS patients were included. Baseline median expanded disability status scale [2.0 (IQR 1.5)] was unchanged during follow-up, 71 % were progression-free, 33 % achieved no evidence of disease activity-3 (NEDA-3). Between baseline and month 60, SyMRI showed a reduction of brain parenchymal fraction (BPF) and grey matter (GM) volume in patients. The BPF reduction was greater in RRMS patients than in SCs (p < 0.05), and more pronounced in patients with high pre-baseline disease activity than in those without (p < 0.01). OCT showed significant thinning of macular ganglion cell and inner plexiform layers (mGCIPL) and in peripapillary retinal nerve fiber layer (pRNFL) in patients. In contrast, absolute values of white matter (WM) volume and myelin content (MyC) quantified by SyMRI, were stable or increased after re-baseline (month 24) and up to month 60, and this increase appeared limited to patients without high pre-baseline disease activity and to patients with NEDA-3 or disability worsening during follow-up. A strong positive correlation between WM volume and GM volume at baseline was lost after ALZ intervention for their delta values, i.e., change from re-baseline (month 24) to month 60. While the positive baseline correlation between WM volume and MyC increased for their delta values, the positive baseline correlation between GM volume and MyC changed to negative for their delta values. CONCLUSION: We showed that neurodegeneration continued in RRMS patients under ALZ treatment, but it appeared to be limited to BPF and GM, and more pronounced in patients with disease activity. Our data suggest that patients who respond to ALZ treatment show signs of remyelination. OCT and SyMRI have potential to quantify measures of neurodegeneration that is affected by treatment intervention in RRMS.

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Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury, and serum glial fibrillary acidic protein (sGFAP) reflects reactive astrogliosis. In adult multiple sclerosis (MS), sNfL correlates with relapsing disease activity while sGFAP correlates with progressive disease. Objectives: We evaluate sNfL and sGFAP as biomarkers in pediatric-onset MS (POMS) compared to pediatric healthy controls (PHC), and correlations with the disease course. Methods: In this single-center observational cross-sectional study, we extracted data from a longitudinal database and measured NfL and GFAP from bio-banked serum using single-molecule array technology. Results: The analysis included 61 POMS patients and 45 PHC. Controlling for age and BMI, sNfL was 414% higher and sGFAP was 42.3% higher in POMS. Disability (EDSS) is associated with higher sNfL (ß = 0.32, p = 0.002) and higher sGFAP (ß = 0.11, p = 0.03). sNfL is associated with MRI lesion burden, recent disease activity (ß =0.95, p < 0.001), and untreated status (ß = 0.5, p = 0.006). Conclusion: sNfL and sGFAP are elevated in POMS compared to PHC. Both biomarkers are associated with clinical disability. Elevated sGFAP may reflect early neurodegeneration in POMS, while sNfL reflects disease activity and DMT response. Elevated sNfL among some clinically and radiographically stable POMS patients suggests ongoing neuroaxonal injury with a potential role for sNfL monitoring disease stability.

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BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. RESULTS: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (ß = 0.25, p = .034 and ß = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). CONCLUSION: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

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BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n=76) or mild cognitive impairment (n=75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Linear regression and ROC analyses were used to address the associations of interest. RESULTS: Higher GFAP levels were associated with NPS at baseline (ß=0.23, p=.008). Higher NfL and GFAP levels were associated with the presence of NPS at follow-up (ß=0.29, p=.007 and ß=0.28, p=.007, respectively) and with an increase in the NPI-Q severity score over time (ß=0.23, p=.035 and ß=0.27, p=.011, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.73 to 0.84, p=.007) and AD pathology (AUC 0.79 to 0.86, p=.006), but not of cognitive decline (AUC 0.79 to 0.84, p=.068). CONCLUSION: Plasma GFAP is associated with NPS while NfL and GFAP are both associated with future NPS and NPS severity. Considering the presence of NPS along with blood-based AD-biomarkers may improve diagnosis and prediction of clinical progression of NPS and inform clinical decision-making in non-demented older people.

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Objective To establish an auxiliary method for diagnosis of mild traumatic brain injury based on serum GFAP rapid detection test strips using immunochromatographic technology labeled with quantum dot microspheres.Methods The quantum dot microspheres were coupled with GFAP antibodies.The detection conditions were optimized to obtain the fluorescence probe in order to prepare the immunochromatographic test strips.An auxiliary diagnostic method was established after optimization of detection conditions.Finally,the auxiliary diagnostic effect of the test strips was evaluated using clinical samples.Results The serum concentration of GFAP could be detected by the optimized test strips within 13 mins with a detection limit of 0.15 ng/mL,and no more than 70μL of the serum sample was required.In addition,good reproducibility was achieved by different batches of test strips(CV=10.7%).The detection sensitivity and specificity of the strips to mild traumatic brain injury using 51 clinical samples were 95.24%and 96.67%respectively,indicating good effects of detection.Conclusion The developed test strips are user-friendly with reliable results,which can facilitate field rapid diagnosis of mild traumatic brain injury in complicated wartime environments.

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AIMS: The present study was developed to investigate how litter reduction-induced obesity promotes early depressive-related behaviors in rodent offspring. MAIN METHODS: We employed a standardized litter size reduction protocol, dividing litters into groups: normal litters (NL), consisting of six males and six females pups and small litters (SL), comprising two males and two females pups. Maternal behavior was monitored during the initial week of lactation. Subsequently, we assessed the pups for weight gain, locomotor activity, social play behavior, and performance in forced swimming test. We further evaluated the weights of retroperitoneal and perigonadal fat tissues, along with the expression of glial fibrillary acidic pprotein (GFAP) in the hippocampus and prefrontal cortex of the offspring. KEY FINDINGS: Our results indicated that litter size reduction led to an increased the maternal behavior. In contrast, offspring from the SL group displayed greater weight gain and increased, retroperitoneal and perigonadal fat. Both male and female rodents in the SL group exhibited decreased social play behavior, and male offspring spent more time immobile during the forced swimming test, suggesting a depressive-like phenotype. Notably, we observed an increase in the GFAP expression in the prefrontal cortex of male rodents, with a trend toward increased expression in the hippocampus. SIGNIFICANCE: Obesity may facilitate the development of early depressive-like behaviors, potentially associated with elevated GFAP expression in the prefrontal cortex.

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Despite its devastating disease burden and alarming prevalence, the etiology of Parkinson's disease (PD) remains to be completely elucidated. PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and this correlates with the accumulation of misfolded α-synuclein. While the aggregation of α-synuclein in the form of Lewy bodies or Lewy neurites is a well-established intraneuronal hallmark of the disease process, our understanding of the glial contribution to aberrant α-synuclein proteostasis is lacking. In this regard, restoring astrocyte function during early PD could offer a promising therapeutic avenue and understanding the involvement of astrocytes in handling/mishandling of α-synuclein is of particular interest. Here, we explore the growing body of scientific literature implicating aberrant astrocytic α-synuclein proteostasis with the seemingly inexorable pathological sequelae typifying PD. We also provide a perspective on how heterogeneity in the morphological relationship between astrocytes and neurons will need to be considered in the context of PD pathogenesis.

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Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.

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Objective:To investigate any effect of repeated transcranial magnetic stimulation (rTMS) on the expression of P2X7 receptor (P2X7R) and glial fibrillary acid protein (GFAP) in the prefrontal cortex and hippocampus of mice modeling depression.Methods:Thirty C57BL/6 mice were divided into a control group ( n=10) and a depression group ( n=20). The mice of the control group were raised in group (five mice per cage), while those of the depression group were kept alone for six weeks to induce depression. Among them, 16 were successfully modeled and randomly divided into a model group ( n=8) and an rTMS group ( n=8). The rTMS group received five sessions per week of 10Hz rTMS for 4 weeks. Any changes in depression-like behavior were observed and the expression of P2X7R and GFAP in the prefrontal cortex and hippocampus was measured. Results:Compared to the control group, a significant decrease was observed in the sucrose consumption rate in the sucrose preference test, in the distance moved in the open field test and in the expression of GFAP protein. But there was a significant increase in the immobile time in the tail suspension test and in the expression of P2X7R protein in the prefrontal cortex and hippocampus in the model group. At the conclusion of the experiment the differences in the sucrose consumption rate, the distance moved, GFAP protein expression, immobile time and P2X7R protein expression between the rTMS and the model group were all statistically significant.Conclusion:rTMS can reduce depression-like behavior, at least in mice. That may be related to inhibiting P2X7R expression and promoting GFAP expression in the prefrontal cortex and hippocampus.

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Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.

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Purpose: The recent increase in aluminum exposure and its effect on the development of the brain call for serious attention. The study investigated the behavioral and immunohistochemical changes in the cerebral cortex of Wistar rats following prenatal co-administration of ethyl acetate leaf fraction of Tamarindus indica (EATI) and aluminum chloride (AlCl3). Methods: Pregnant Wistar rats were divided into 5 groups (n=4). Group I (negative control), Group II-V were experimental groups treated with 200 mg/kg of AlCl3 s/c. Group III and IV received an additional 400 mg/kg and 800 mg/kg of EATI respectively, while Group V received an additional 300 mg/kg of Vitamin E for 14 days (prenatal days 7-21) via the oral route. The pups were then exposed to cliff avoidance, negative geotaxis, and elevated plus maze (EPM) test on the post-natal day (PoND) 4-6, 7-10, and 18 respectively. On PoND 21 pups were sacrificed, and the skull dissected to remove the brain. The harvested brain tissues were processed for Cresyl fast (CF) and glial fibrillary acid protein (GFAP). Results: The study showed that EATI administration during AlCl3 exposure was associated with significant improvement in sensory-motor development. The EPM, CF, and GFAP results revealed significant improvement in anxiety-like behavior, motor activities, GFAP expression, pyramidal cell count, and Nissl staining following prenatal EATI administration during AlCl3 exposure. Conclusion: The present study concludes that EATI was associated with some protective potential during prenatal AlCl3 exposure in Wistar rats.

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Many studies conducted after the pandemic period revealed that, while COVID-19 primarily injured the lungs, it also affects other organs in the form of cardiovascular complications, metabolic derangements, renal damage, and so on. Although we know that inflammatory cascades, complement activation, and pro-inflammatory cytokines are all involved in vasculitic processes that cause organ damage, we do not know the exact mechanism of complications such as acute respiratory distress syndrome (ARDS), cardiovascular ischemia, deep vein thrombosis, pulmonary thromboembolism, and brain injuries (embolism) that are frequently observed in COVID 19. The currently available biomarkers do not predict the severity of the aforementioned complications. As a result, more specific biomarkers such as serum calcium binding protein (S100B), glial fibrillary acid protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), hs-TNI, (highly sensitive cardiac troponin) - HBDH, (Hydroxybutyrate Dehydrogenase), CK-MB (creatine kinase myocardial band), ST2 (suppression of tumorigenicity 2) are in need for early detection & improved clinical outcome.

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The term neuromyelitis optica spectrum disorder (NMOSD) describes a group of clinical-MRI syndromes characterized by longitudinally extensive transverse myelitis, optic neuritis, brainstem dysfunction and/or, less commonly, encephalopathy. About 80% of patients harbor antibodies directed against the water channel aquaporin-4 (AQP4-IgG), expressed on astrocytes, which was found to be both a biomarker and a pathogenic cause of NMOSD. More recently, antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), have been found to be a biomarker of a different entity, termed MOG antibody-associated disease (MOGAD), which has overlapping, but different pathogenesis, clinical features, treatment response, and prognosis when compared to AQP4-IgG-positive NMOSD. Despite important refinements in the accuracy of AQP4-IgG and MOG-IgG testing assays, a small proportion of patients with NMOSD still remain negative for both antibodies and are called "seronegative" NMOSD. Whilst major advances have been made in the diagnosis and treatment of these conditions, biomarkers that could help predict the risk of relapses, disease activity, and prognosis are still lacking. In this context, a number of serum and/or cerebrospinal fluid biomarkers are emerging as potentially useful in clinical practice for diagnostic and treatment purposes. These include antibody titers, cytokine profiles, complement factors, and markers of neuronal (e.g., neurofilament light chain) or astroglial (e.g., glial fibrillary acidic protein) damage. The aim of this review is to summarize current evidence regarding the role of emerging diagnostic and prognostic biomarkers in patients with NMOSD and MOGAD.

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There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.

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BACKGROUND: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. OBJECTIVE: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. STUDY DESIGN: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. RESULTS: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64-2.88), 2.17-fold higher tau (95% confidence interval, 1.49-3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06-3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92-4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06-5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06-2.55), tau (4.44-fold higher; 95% confidence interval, 1.85-10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32-2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. CONCLUSION: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.

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We herein report a 47-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) revealed by periventricular radial linear enhancement on repeated brain magnetic resonance imaging (MRI). He presented with a history of headache and a fever followed by somnolence and worsening of consciousness. On admission (16 days from the onset), although lymphocytic pleocytosis and hypoglycorrhachia in the cerebrospinal fluid (CSF) were noted, initial brain MRI demonstrated non-specific findings. At 30 days from the onset, repeated brain MRI revealed characteristic findings of GFAP-A, and we detected anti-GFAP antibodies in the CSF. Thus, repeated brain MRI provides clues for the diagnosis of GFAP-A.

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Background: Astrocytes and microglia play an important role in the inflammatory process of multiple sclerosis (MS). We investigated the associations between the cerebrospinal fluid (CSF) levels of glial fibrillary acid protein (GFAP) and soluble triggering receptors expressed on myeloid cells-2 (sTREM-2), inflammatory molecules, and clinical characteristics in a group of patients with relapsing-remitting MS (RRMS). Methods: Fifty-one RRMS patients participated in the study. Clinical evaluation and CSF collection were performed at the time of diagnosis. The CSF levels of GFAP, sTREM-2, and of a large set of inflammatory and anti-inflammatory molecules were determined. MRI structural measures (cortical thickness, T2 lesion load, cerebellar volume) were examined. Results: The CSF levels of GFAP and sTREM-2 showed significant correlations with inflammatory cytokines IL-8, G-CSF, and IL-5. Both GFAP and sTREM-2 CSF levels positively correlated with age at diagnosis. GFAP was also higher in male MS patients, and was associated with an increased risk of MS progression, as evidenced by higher BREMS at the onset. Finally, a negative association was found between GFAP CSF levels and cerebellar volume in RRMS at diagnosis. Conclusions: GFAP and sTREM-2 represent suitable biomarkers of central inflammation in MS. Our results suggest that enhanced CSF expression of GFAP may characterize patients with a higher risk of progression.

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Radial glial cells (RGCs) play an essential role in developing, maintaining, and repairing the central nervous system (CNS). However, a specific reporter line of RGCs is limited in medaka. Glial fibrillary acid protein (GFAP) is abundant in teleost CNS, including the brain and spinal cord, and is a possible candidate for a marker for RGCs in medaka CNS. We generated a transgenic medaka in which enhanced green fluorescent protein (EGFP) expression is regulated under putative medaka gfap regulatory elements. We observed EGFP expression in the CNS of live larval and juvenile medaka through the transparent body of the See-through medaka strain. Histological analysis for juvenile and adult Tg(gfap:EGFP) medaka showed that EGFP was expressed in GFAP-positive cells in the telencephalon, optic tectum, retina, and spinal cord. We further found another EGFP expressing cells in the optic tectum and retina. These cells are possibly neuroepithelial-like stem cells, deducing from the distribution of these EGFP-positive cells. We concluded that this reporter line would be valuable in the investigation of neural stem cell function during the development and regeneration of medaka CNS visualizing two types of neural stem cells, RGCs and neuroepithelial-like stem cells.

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BACKGROUND: The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. OBJECTIVE: The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. METHODS: Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. RESULTS: The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). CONCLUSION: The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.

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Objective:To investigate the inhibitory effect of specific inhibitor of necroptosis necrostatin-1 (Nec-1) on necroptosis of retinal ganglion cells (RGCs) in rats with acute ocular hypertension.Methods:Twenty-four adult male Sprague Dawley rats were randomly divided into normal control group, model control group, Nec-1 treatment group and negative control group by random number table method, with 6 rats in each group.High intraocular pressure (IOP)-induced ischemia and reperfusion model was established through anterior chamber irrigation of 0.9% sodium chloride solution in left eyes of the rats, raising the IOP to 110 mmHg (1 mmHg=0.133 kPa) for 60 minutes.Nec-1 (4 mmol/L, 2 μl) or dimethyl sulfoxide (2 μl) was intravitreally injected immediately in Nec-1 treatment group and negative control group following modeling, respectively, according to grouping.No intervention was administered to the normal control group.Paraffin sections of rat retinas of the left eyes in different groups were prepared seven days after modeling.The retinal structure was observed by hematoxylin-eosin staining, and the expression levels of thymocyte antigen-1 (Thy-1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemical staining.All animal experiments were approved by an Ethics Committee of Tianjin Union Medical Center (No.2017 Quick audit C01).Results:Seven days after modeling, compared with normal control group, the retinal nerve fiber layer was thinner in model control group and negative control group, and the RGCs were arranged loosely, and cells in the inner nuclear layer were reduced and arranged disorderly, and cells in the outer nuclear layer were normal or enlarged.Compared with model control group and negative control group, the nerve fiber layer was thickened and the number of RGCs was significantly increased in Nec-1 treatment group.The number of Thy-1-positive RGCs was decreased in model control group, negative control group and Nec-1 treatment group than normal control group, and there were more Thy-1-positive RGCs in Nec-1 treatment group than model control group and negative control group.The integrated absorbance ( A) value of GFAP protein in normal control group, model control group, negative control group and Nec-1 treatment group was 47.209±15.311, 116.220±18.194, 116.382±19.020, 92.818±10.236, respectively, showing statistically significant differences among them ( F=24.675, P<0.001). The integrated A value of GFAP protein was significantly increased in model control group, negative control group and Nec-1 treatment group than normal control group, and the integrated A value of GFAP protein in Nec-1 treatment group was lower than that in model control group and negative control group, with statistically significant differences (all at P<0.05). Conclusions:Nec-1 can promote RGCs survival by inhibiting the necroptosis of RGCs in rats with acute intraocular hypertension.