Search Results (266)

Background: Multiple studies of the role of neurotransmitter systems in the effects of various substances on brain functions under normal conditions and at various brain disorders have demonstrated the relatively high usefulness of the electroencephalogram (EEG). However, little is known about EEG “fingerprints” of direct neurotransmitter–receptor interactions, in particular, for monoamine (MA) systems involved in the main brain functions. Methods: We looked at how the EEG effects of serotonin, dopamine, and norepinephrine receptors activating substances (quipazine, SKF-38393, and clonidine, respectively) injected into the brain’s lateral ventricles were affected by corresponding blockers (cyproheptadine, SCH-23390, and yohimbine) in freely moving rats. We introduced a method for clustering significant changes in the EEG spectra based on specific time intervals and narrow frequency subranges. Results: Stimulating serotonin and dopamine receptors caused specific suppression of EEG activity around 10 Hz and an increase near 18 Hz, respectively. The effects were reduced after pretreatment with the corresponding receptor blockers. Clonidine produced clusters of increased and decreased EEG activity around 6 Hz and 21 Hz, respectively, which were weakened by the blocker, yohimbine. These results demonstrate the “signatures” of different MA systems in EEG time–frequency clustering. Conclusions: We consider the developed approach as a potentially useful tool in clinics for evaluation of MA transmission pathology and its therapy with corresponding substances penetrating the blood–brain barrier. Full article

Bluetongue is a vector-borne viral infectious disease primarily affecting ruminants, transmitted by biting midges of the Culicoides species. The first bluetongue virus 3 (BTV-3) cases occurred in Hesse, Germany, in July 2024. From December 2024 onwards, field veterinarians observed calves born with neurological symptoms. A convenience sample of affected calves were admitted to the Veterinary Teaching Hospital at Justus-Liebig-University Giessen, Germany. A total of 13 calves from unvaccinated dams with pronounced neurological symptoms and positive PCR results for BTV-3 were studied. General and neurological examinations were performed and a blood sample was obtained for hematologic, blood biochemical and blood gas analysis. In 11 calves, magnetic resonance imaging (MRI) was performed. Due to the severe neurological lesions, all calves were euthanized and postmortem examinations were performed. The neurological examination of the calves revealed neurological indications consistent with diffuse forebrain disease. MRI revealed that all calves exhibited various stages of cortical parenchyma cell loss and secondary enlargement of the lateral ventricles. Postmortem examination revealed moderate to severe hydrocephalus internus or hydranencephaly. The results of clinical and neurological examinations, MRI, and postmortem examination, indicate severe impairment of brain development presumably associated with transplacental BTV-3 infection. Epidemiologic data and health records from the originating farms suggest that neurologic malformations developed after BTV-3 infection between 95 and 227 of the gestation period. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL. Full article

Background and Objectives: The objective of this research is to make a comparative evaluation of the correlation between the volumetric examination of subcortical cerebral regions and white matter hyperintensities classified according to the Fazekas scoring system. Materials and Methods: A total of 236 cases with cranial MRI studies were retrospectively analyzed. This study included patients aged over 45 years who had white matter hyperintensities and who did not have a prior stroke diagnosis. White matter hyperintensities were evaluated in axial FLAIR images according to Fazekas’s grading scale. Patients with Fazekas 0 and 1 were grouped in group 1 and the patients with Fazekas 2 and 3 were grouped in group 2. MRI data processing and subcortical volumetric analyses were performed using the volBrain MRI brain volumetry system. Results: There were statistically significant differences between groups 1 and 2 in terms of cerebrospinal fluid total brain white and gray matter (p < 0.001), total brain white and gray matter (p = 0.009), total cerebrum (p < 0.001), accumbens (p < 0.001), thalamus (p < 0.001), frontal lobe (p < 0.001), parietal lobe (p < 0.001), and lateral ventricle (p < 0.001) volumes. Conclusions: Our study finds a strong link between white matter hyperintensity burden and brain atrophy. This includes volume reductions in total brain white and gray matter, frontal and parietal lobe atrophy, increased cerebrospinal fluid (CSF), and atrophy in specific brain regions such as the accumbens and thalamus. Full article

Glial cells, once considered mere support for neurons, have emerged as key players in brain function across vertebrates. The historical study of glia dates to the 19th century with the identification of ependymal cells and astrocytes, followed by the discovery of oligodendrocytes and microglia. While neurocentric perspectives overlooked glial functions, recent research highlights their essential roles in neurodevelopment, synapse regulation, brain homeostasis, and neuroimmune responses. In teleost fish, a group comprising over 32,000 species, glial cells exhibit unique properties compared to their mammalian counterparts. Thus, the aim of this review is synthesizing the current literature on fish glial cells, emphasizing their evolutionary significance, diversity, and potential as models for understanding vertebrate neurobiology. Microglia originate from both yolk sac cells and hematopoietic stem cells, forming distinct populations with specialized functions in the adult brain. Neural stem cells, including radial glial cells (RGCs) and neuroepithelial cells, remain active throughout life, supporting continuous neuro- and gliogenesis, a phenomenon far more extensive than in mammals. Ependymocytes line brain ventricles and show structural variability, with some resembling quiescent progenitor cells. Astrocytes are largely absent in most fish species. However, zebrafish exhibit astrocyte-like glial cells which show some structural and functional features in common with mammalian astrocytes. Oligodendrocytes share conserved mechanisms with mammals in myelination and axon insulation. Full article

Background and Aims: Vitamin D is currently well regarded for its pleiotropic effects on the immune system, stimulating an anti-inflammatory response and enhancing immune tolerance. Vitamin D deficiency is an established risk factor for multiple sclerosis (MS). Additionally, lower vitamin D serum levels are associated with worse disease outcomes. However, current randomized clinical trials provide conflicting evidence about the beneficial role of vitamin D on disease progression. Most studies have evaluated the effect of vitamin D supplementation on clinical and radiological activity, yet very few have examined the impact on brain atrophy. Methods: A 4-year observational, non-interventional study design was applied to evaluate the association between vitamin D supplementation and disease progression. Altogether, 132 relapsing–remitting multiple sclerosis patients were enrolled in the study (97 subjects in the group with vitamin D supplementation and 35 subjects in the group without supplementation). The analyzed groups were similar in terms of age, body mass index, sun exposure, comorbidities, nicotinism, duration of the disease, and current treatment. The number of relapses, Expanded Disability Status Scale assessments, and the number of new/enlarged T2-weighted lesions and gadolinium-enhancing lesions in magnetic resonance imagining analyses, as well as 25-hydroxyvitamin D serum levels, were assessed every 12 months of a 4-year follow-up, whereas brain atrophy was assessed at the baseline and after 36 months using two-dimensional measurements. Results: After 36 months, a significant increase in atrophy was observed in both groups; however, patients without vitamin D supplementation had a significantly higher increase in intercaudate distance, third ventricle width, and bicaudate ratio after 36 months of observation (p < 0.05). Vitamin D supplementation among the studied group did not affect other disease activity outcomes. Conclusions: Our study revealed an observed association between vitamin D supplementation and reduced brain atrophy in patients with MS. Randomized controlled trials are required to establish the impact of vitamin D supplementation on brain atrophy progression. Full article

Background/Objectives: Artificial intelligence (AI) models for Alzheimer’s disease (AD) diagnosis often face the challenge of limited explainability, hindering their clinical adoption. Previous studies have relied on full-scale MRI, which increases unnecessary features, creating a “black-box” problem in current XAI models. Methods: This study proposes an explainable ensemble-based diagnostic framework trained on both clinical data and mid-slice axial MRI from the ADNI and OASIS datasets. The methodology involves training an ensemble model that integrates Random Forest, Support Vector Machine, XGBoost, and Gradient Boosting classifiers, with meta-logistic regression used for the final decision. The core contribution lies in the exclusive use of mid-slice MRI images, which highlight the lateral ventricles, thus improving the transparency and clinical relevance of the decision-making process. Our mid-slice approach minimizes unnecessary features and enhances model explainability by design. Results: We achieved state-of-the-art diagnostic accuracy: 99% on OASIS and 97.61% on ADNI using clinical data alone; 99.38% on OASIS and 98.62% on ADNI using only mid-slice MRI; and 99% accuracy when combining both modalities. The findings demonstrated significant progress in diagnostic transparency, as the algorithm consistently linked predictions to observed structural changes in the dilated lateral ventricles of the brain, which serve as a clinically reliable biomarker for AD and can be easily verified by medical professionals. Conclusions: This research presents a step toward more transparent AI-driven diagnostics, bridging the gap between accuracy and explainability in XAI. Full article

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurosteroids, including allopregnanolone (ALLO), play critical roles in modulating neuronal activity in the brain. Levels of these compounds dynamically fluctuate in response to physiological and environmental conditions, particularly stress, suggesting complex regulatory interactions. This study aimed to explore the effects of acute stress and ALLO (individually and combined) on hippocampal expression of BDNF, its TrkB receptor, and other neurotrophins in sheep, a translational large animal model. Adult, luteal-phase sheep (n = 24), implanted with a guide cannula into the third brain ventricle, were divided into four experimental groups: (i) 3 days of Ringer–Locke solution (RL) infusion as the control; (ii) 3 days of RL infusion with 4 h acute stress on day three; (iii) 3 days of ALLO infusion (4 × 15 µg/60 µL/30 min) with 4 h acute stress on day three; and (iv) 3 days of ALLO infusion alone (n = 6 per group). Both acute stress and ALLO alone significantly reduced BDNF concentration and BDNF transcript abundance in the hippocampal CA1 and CA3 fields compared to the control group. The combined application of both stress and ALLO resulted in decreased levels of these parameters, except for BDNF concentration in the CA3 region. Additionally, TrkB mRNA expression in both hippocampal fields was significantly reduced in all treatment groups. Changes in mRNA levels for other neurotrophins, including nerve growth factor (NGF) and neurotrophin 3 (NT3) and 4 (NT4), varied under experimental conditions. While an inhibitory effect was predominant, NGF expression in the CA1 region remained unaffected by stress or ALLO. Interestingly, stress alone induced a significant increase in NT4 mRNA expression in the CA3 field compared to the control. In conclusion, the study demonstrated that a 4 h acute stress exposure inhibited the synthesis of BDNF, TrkB, and several other neurotrophins in the sheep hippocampus. Furthermore, ALLO, whose increased levels are highly correlated with the initial stress response, may serve as a mediator of this stress effect, temporarily preventing over-stimulation of hippocampal BDNF release and signaling. Full article

The area postrema (AP) is a circumventricular organ (CVO) at the base of the fourth ventricle. It has a crucial role in regulating nausea and vomiting due to its unique blood–brain barrier (BBB)-permeability and extensive neural connectivity. Here, we present two cases of area postrema syndrome (APS), a rare condition of intractable nausea and vomiting resulting from direct AP injury. Our cases each occurred in the context of infratentorial neoplasms or their treatment. Using these cases as a framework, we review the literature on central emetic pathways and propose a treatment algorithm for managing refractory nausea and vomiting of central origin. We also highlight other targets beyond conventional serotonergic, dopaminergic, or histaminergic blockade and their roles in central hyperemesis. Our literature review suggests that APS is due to the disruption of the baseline inhibitory tone of outgoing AP signals. When other options fail, our algorithm culminates in the off-label use of combined serotonergic and neurokinin-1 blockade, which is otherwise used to manage chemotherapy-induced nausea and vomiting (CINV). We believe multimodal CNS receptor blockade is efficacious in APS because it addresses the underlying central neural dysregulation, rather than solely targeting peripheral emetic triggers. Full article

Background/Objectives: The percutaneous insertion of an external ventricular drain (EVD) is a common neurosurgical procedure that is crucial in managing acute brain injuries because of the drain’s role in monitoring intracranial pressure and draining cerebrospinal fluid. The primary indication is acute hydrocephalus, which often results from subarachnoid hemorrhage, intracranial hemorrhage, traumatic brain injury, stroke, or infection. Standard EVD placement targets the frontal horn of the lateral ventricle. However, complications such as hemorrhage, infection, and catheter occlusion frequently arise, with occlusion rates ranging from 19% to 47%. Occlusion can lead to increased intracranial pressure, necessitating interventions such as saline flushes or fibrinolytic drug administration. The placement of an EVD is a very specific choice that must be tailored to the individual patient, often in scenarios in which multiple interpretations of the data are possible: the question of which patient is eligible for EVD placement may be subjective. Intraventricular fibrinolysis (IVF) with urokinase-type plasminogen activator (uPA) or tissue-type plasminogen activator is used with the aim of lysing intraventricular clots and preventing EVD occlusion. Despite numerous studies, conclusive evidence on their efficacy is lacking. The CLEAR III trial confirmed the safety of IVF but showed uncertain benefits in neurological outcomes. Given the limited literature on uPA, this study evaluates its intrathecal administration for the prevention of EVD occlusion. Not all therapies are appropriate for all patients, and customizing strategies is often the right way to get the best result. Methods: This retrospective study analyzed 20 patients with EVDs receiving intrathecal uPA. The patients had a mean age of 56.4 years, with 95% presenting with hydrocephalus and 80% presenting with intraventricular hemorrhage. uPA dosages varied (25,000–100,000 IU), with an average of 3.9 doses per patient. Results: IVF effectively maintained EVD patency in 95% of cases. One patient experienced asymptomatic bleeding, while four (20%) developed post-treatment infections, the development of which was potentially influenced by the prolonged duration of EVD retention (>21 days). Analysis of Graeb scores showed faster clot resolution with early uPA administration. A higher initial Graeb score correlated with increased total uPA load but not with mortality or discharge outcomes. Although infection rates were slightly higher than in CLEAR III, multiple confounding factors, including duration of EVD retention and bilateral placement, were present. Conclusions: This study supports the feasibility and safety of intrathecal uPA administration for management of EVD occlusion in certain contexts. The appropriate choice in the context of ‘personalized medicine’ must necessarily consider the risk–benefit ratio. Full article

Objective: Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, MPDZ variants have been reported to cause severe ventriculomegaly inherited in an autosomal recessive manner (OMIM#615219). Several hypotheses have been put forward linking MPDZ variants to ventriculomegaly, but the precise underlying mechanisms, in particular whether its origin is obstructive or non-obstructive, are yet to be elucidated. Methods: To address this question, we retrospectively analyzed pre- and postnatal neuro-imaging and neuropathological data for cases of ventriculomegaly in which MPDZ variants were found through exome or genome sequencing. We performed anti-MPDZ immunostaining on fetal brain samples. Results: We analyzed six cases (four fetuses and two children) of ventriculomegaly of variable severities with MPDZ variants. The precise analysis of brain MRI data, corroborated by fetopathological examinations, demonstrated an obstructive pattern of ventriculomegaly upstream from partial fusion of the thalami, also called diencephalosynapsis, with partial atresia of the third ventricle, which could extend to Sylvius’s aqueduct. Conclusions: The morphological analysis using targeted brain magnetic resonance imaging (MRI) and neuropathological data allowed us to unravel the underlying mechanisms of congenital ventriculomegaly related to MDPZ variants. Full article

Bacillus Calmette–Guerin (BCG) central nervous system (CNS) infections are one of the rarest complications following BCG exposure. A 77-year-old male, with bladder cancer previously treated with BCG instillation, presented with fever, confusion, and brain magnetic resonance imaging (MRI) consistent with encephalitis one month after the last BCG instillation. Cerebrospinal fluid (CSF) showed marked hypoglycorrhachia, hyperproteinorrachia, and lymphocytic pleocytosis. Despite CSF culture negativity, the presentation was considered suggestive of BCG-related encephalitis, and the empirical standard antitubercular treatment (rifampin, isoniazid and ethambutol), plus dexamethasone, was initiated. Following initial improvement, gait ataxia and hemiplegia were observed at the 4-month follow-up. MRI revealed an excluded enlarged left lateral ventricle with signs of ventriculitis, requiring surgical drainage. CSF collected during neurosurgery resulted positive on PCR for M. tuberculosis complex. Adjunctive linezolid was initiated, replaced by levofloxacin due to adverse events after 2 weeks. The patient was discharged following a normal CSF analysis. Oral antitubercular therapy was prescribed for 14 months and there were no signs of relapse at the 24-month follow-up. Previously, 16 cases of CNS BCGitis have been reported, without any cases of clinical relapse during antitubercular treatment. Furthermore, our study reports the use of linezolid as a 4th antitubercular drug for CNS BCGitis. Full article

Background/Objectives: Hyperexcitable neuronal activity associated with seizures may disrupt brain homeostasis resulting in abnormal glucose and nutrient management and metabolism. Specialized ependymal cells known as tanycytes line the third ventricle wall bridging communication between the brain, CSF, and blood. Despite their positional importance, whether tanycytes are impacted by epilepsy is unknown. Here, known protein markers of tanycytes were assessed in the Kcna1-null mouse model of genetic epilepsy with spontaneous recurrent seizures (SRS mice). Further, whether an anti-seizure metabolic ketogenic diet (KD), previously proven effective in SRS mice, restored protein levels was determined. Methods: Known tanycyte proteins, including glucose transporter 1 (GLUT1), glial fibrillary acidic protein (GFAP), and doublecortin (DCX, to determine potential neurogenic differences) were examined throughout the anterior–posterior axis of the third ventricle using immunofluorescent histochemistry. Results: Decreased GLUT1 immunoreactivity and elevated GFAP levels were found in the SRS cohorts. The number of neurogenic DCX-expressing cells did not differ. Two weeks of KD treatment reduced GFAP to WT levels. GLUT1 remained low in KD-treated SRS mice. Conclusions: These data suggest that the expression of proteins important for the structure and function of tanycytes is altered in preclinical epilepsy and is differentially restored with KD treatment. Whether tanycytes actively participate in the pathophysiology of epilepsy or associated comorbidities is an intriguing possibility given their integral role in brain homeostasis. Full article

Background/Objective: The accurate diagnosis of congenital central nervous system abnormalities is critical to pre- and postnatal prognostication and management. When an abnormality is found in the posterior fossa of the fetal brain, parental counseling is challenging because of the wide spectrum of clinical and neurodevelopmental outcomes in patients with Dandy–Walker (DW) spectrum posterior malformations. The objective of this study was to evaluate the utility of biometric measurements obtained from fetal magnetic resonance imaging (MRI) to facilitate the prenatal differentiation of Dandy–Walker (DW) spectrum malformations, including vermian hypoplasia (VH), Blake’s pouch cyst (BPC), and classic Dandy–Walker malformation (DWM). Methods: This retrospective single-center study evaluated 34 maternal–infant dyads referred for fetal MRI evaluation of suspected DW spectrum malformations identified on antenatal ultrasound. Radiologists took posterior fossa measurements, including the vermis anteroposterior (AP) diameter, vermis height (VH), and tegmento–vermian angle (TVA). The posterior fossa, fourth ventricle, and cisterna magna were classified as normal, large, or dilated. The postnatal imaging findings were evaluated for concordance. The acquired values were compared between the groups and with normative data. The genetic testing results are reported when available. Results: A total of 27 DW spectrum fetal MRI cases were identified, including 7 classic DWMs, 14 VHs, and 6 BPCs. The TVA was significantly higher in the DWM group compared with the VH and BPC groups (p < 0.001). All three groups had reduced AP vermis measurements for gestational age compared with normal fetal brains, as well as differences in the means across the groups (p = 0.002). Conclusions: Biometric measurements derived from fetal MRI can effectively facilitate the prenatal differentiation of VH, BPC, and classic DWM when assessing DW spectrum posterior fossa lesions. Standardizing biometric measurements may increase the diagnostic utility of fetal MRI and facilitate improved antenatal counseling and clinical decision-making. Full article

The composition of genomic mediators of glucocorticoid actions in the brain remains elusive because of low-statistical-power experiments and the associated transcriptomic data with very low consistency. The problem is further exaggerated by the underrepresentation of chronic experiments and the interpretation of differentially expressed genes without understanding their contribution to the total transcriptomic activity. To fill existing gaps in knowledge, we have performed a large transcriptomic experiment, testing the effects of prolonged treatment with corticosterone on the hippocampal transcriptome (RNA sequencing). The experiment showed that prolonged treatment with corticosterone induced a set of transcriptomic effects that were replicable across treatment durations, including genes relevant for human PTSD (Opalin, Pllp, Ttyh2, Lpar1) and prolonged stress in animals (Cnp, Fam163a, Fcrls, Tmem125). Some of the affected genes are specific for oligodendrocytes, neurons, astrocytes, immune cells, the vascular system, and brain ventricles, indicating that glucocorticoids may affect all central nervous system components. The data also showed that the largest changes in expression of corticosterone-responsive genes are restricted to genes with a relatively low expression level and small contribution to the overall pool of mRNAs in the hippocampus. As a result, even a large change in the number of affected genes leads to a small change in the number of newly synthesized mRNA copies. This means, in turn, that the transcriptomic changes induced by corticosterone have low-cost effects on the brain. This specificity of transcriptomic responses also poses a challenge for the interpretation of data and constitutes a potential source of reporting bias in past studies. Therefore, there is a need for further research on products of gene expression, both at the transcriptomic and proteomic levels, during stress conditions. Full article