NeuroSci最新文献

Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are involved in the pathogenesis of Parkinson's disease. The activity of LRRK2 in microglial cells is associated with neuroinflammation, and LRRK2 inhibitors are crucial for alleviating this neuroinflammatory response. α-synuclein contributes to oxidative stress in the dopaminergic neuron and neuroinflammation through Toll-like receptors in microglia. In this study, we investigated the effect of the marine alga Padina arborescens on neuroinflammation by examining LRRK2 activation and the aggregation of α-synuclein. P. arborescens extract inhibits LRRK2 activity in vitro and decreases lipopolysaccharide (LPS)-induced LRRK2 upregulation in BV2, a mouse microglial cell line. Treatment with P. arborescens extract decreased tumor necrosis factor-α (TNF-α) gene expression by LPS through LRRK2 inhibition in BV2. It also attenuated TNF-α gene expression, inducible nitric oxide synthase, and the release of TNF-α and cellular nitric oxide in rat primary microglia. Furthermore, P. arborescens extract prevented rotenone (RTN)-induced oxidative stress in primary rat astrocytes and inhibited α-synuclein fibrilization in an in vitro assay using recombinant α-synuclein and in the differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH). The extract increased lysosomal activity in dSH cells. In addition, P. arborescens extract slightly prolonged the lifespan of Caenorhabditis elegans, which was reduced by RTN treatment.

The burden of simultaneous acute code stroke activation (ACSA) is not known. We aim to assess the effect of simultaneous ACSA on workflow metrics and home time at 90 days in patients undergoing reperfusion therapies in the emergency department. Simultaneous ACSA was defined as code activation within 60 min of the arrival of any patient receiving intravenous thrombolysis, within 150 min of the arrival of any patient receiving endovascular thrombectomy, within 45 min of the arrival of any patient receiving no reperfusion therapies (based on mean local door-to-needle and door-to-puncture times). Simultaneous ACSA was further graded as 1, 2 and 3. We assessed workflow metrics as door-to-CT (DTC) time, in minutes, and functional outcome as home time at 90 days. A total of 2605 patients were assessed as ACSA at a mean ± SD activations of 130.8 ± 17.1/month and 859 (33%) were simultaneous. Among all ACSA, 545 (20.9%) underwent acute reperfusion therapy with a mean age of 70.6 ± 14.2 years, 45.9% (n = 254) were female with a median (IQR) NIHSS of 13 (8-18). A total of 220 (40.4%) patients underwent simultaneous treatments. The median DTC time, in minutes, was prolonged in grade 3 simultaneous ACSA (18 (13, 28)) compared to non-simultaneous ACSA (15 (11, 21) β = 0.23, p < 0.0001). There was no difference in the median home time at 90 days between the simultaneous (58, 0-84.5 days) and non-simultaneous (54, 0-85 days) patients. Simultaneous ACSA is frequent in patients receiving acute reperfusion therapies. An optimal workflow in high-volume centers may help mitigate the clinical and system burden associated with simultaneity.

Autism rates have been reported to be increasing rapidly in industrialized societies. The pathology most often combines neurological symptoms associated with language and social impairments with gastrointestinal symptoms. This study aimed to measure differences in oral metatranscriptome and mitochondrial health between ASD children and neurotypical USA and Colombia ("Blue Zone") children. In addition, this study aimed to determine whether using prebiotics and probiotics would change the oral microbiome and mitochondrial health of ASD children. Buccal swabs and saliva samples were obtained from 30 autistic individuals (USA) at three intervals: prior to intervention, post-prebiotic, and post-probiotic. In addition, a subject component who were neurotypical, which included individuals from the USA (30) and Colombia (30), had buccal swabbing and salivary sampling performed for metatranscriptomic and mitochondrial comparison. Significant differences were observed in the temporal data, demonstrating shifts that interventions with probiotics and polyols may have precipitated. Particular bacterial strains were significantly more prevalent in the autism group, including a strain that reduced neurotransmitter levels via enzymatic degradation. This supports the hypothesis that the microbiome may influence the occurrence and degree of autism. Verbal skills increased in six of the 30 ASD subjects following xylitol and three more after probiotic supplementation, according to both parental reports and the subjects' healthcare providers.

The purpose of the article is to provide a practical guide for manual and semi-automated image segmentation of common neurosurgical cranial lesions, namely meningioma, glioblastoma multiforme (GBM) and subarachnoid haemorrhage (SAH), for neurosurgical trainees and researchers.

Materials and methods: The medical images used were sourced from the Medical Image Computing and Computer Assisted Interventions Society (MICCAI) Multimodal Brain Tumour Segmentation Challenge (BRATS) image database and from the local Picture Archival and Communication System (PACS) record with consent. Image pre-processing was carried out using MRIcron software (v1.0.20190902). ITK-SNAP (v3.8.0) was used in this guideline due to its availability and powerful built-in segmentation tools, although others (Seg3D, Freesurfer and 3D Slicer) are available. Quality control was achieved by employing expert segmenters to review.

Results: A pipeline was developed to demonstrate the pre-processing and manual and semi-automated segmentation of patient images for each cranial lesion, accompanied by image guidance and video recordings. Three sample segmentations were generated to illustrate potential challenges. Advice and solutions were provided within both text and video.

Conclusions: Semi-automated segmentation methods enhance efficiency, increase reproducibility, and are suitable to be incorporated into future clinical practise. However, manual segmentation remains a highly effective technique in specific circumstances and provides initial training sets for the development of more advanced semi- and fully automated segmentation algorithms.

Background: We have previously shown that static and dynamic resting-state functional connectivity differ between migraineurs with and without photophobia, phonophobia, or osmophobia. Furthermore, some patients with photophobia also experience phonophobia or osmophobia. To investigate the functional connectivity specific to migraineurs with photophobia, we examined the differences in static and dynamic resting-state functional connectivity between patients with and without photophobia, with no phonophobia or osmophobia.

Methods: Fifteen migraineurs with photophobia but without phonophobia or osmophobia, as well as 15 sex- and age-matched migraineurs without photophobia, phonophobia, or osmophobia, underwent 3-T functional magnetic resonance imaging during the interictal phase. Static and dynamic resting-state functional connectivity were compared using region-of-interest analyses of 91 cortical, 15 subcortical, and 26 cerebellar areas.

Results: Static resting-state functional connectivity analysis revealed ten significant connectivity pairs in patients with photophobia, while dynamic resting-state functional connectivity analysis revealed six significant connectivity pairs in patients with photophobia. Migraineurs with photophobia had significantly lower connectivity between the cerebellar hemisphere and the temporal region than those without photophobia in both static and dynamic studies.

Conclusions: Our results show that lower resting-state functional connectivity between the cerebellar hemisphere and the temporal region is specific to migraineurs with photophobia.

The maintenance of energetic homeostasis relies on a tight balance between glycolysis and mitochondrial oxidative phosphorylation. The case of the brain is a peculiar one, as although entailing a constant demand for energy, it is believed to rely mostly on glucose, particularly at the level of neurons. Nonetheless, this has been challenged by studies that show that alternatives such as lactate, ketone bodies, and glutamate can be used as fuels to sustain neuronal activity. The importance of fatty acid (FA) metabolism to this extent is still unclear, albeit sustaining a significant energetic output when compared to glucose. While several authors postulate a possible role of FA for the energetic homeostasis of the brain, several others point out the intrinsic features of this pathway that make its contribution difficult to explain in the context of neuronal bioenergetics. Moreover, fueling preference at the synapse level is yet to be uncovered. In this review, we discuss in detail the arguments for and against the brain usage of FA. Furthermore, we postulate that the importance of this fuel may be greater at the synapse, where local mitochondria possess a set of features that enable a more effective usage of this fuel source.

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis.

Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes.

Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center.

Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0-42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0-4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively.

Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.

We develop a frequency domain template subtraction approach to attenuate the maternal ECG in the abdominal ECG measured from pregnant women. The proposed approach was tested on five public fetal ECG datasets simultaneously measured with ECG from the fetal scalp. The method's performance was compared with the template subtraction approach in the time domain using the accuracy and association metrics. The accuracy was calculated by counting the number of fetal complexes in the processed data that coincided with the fetal complexes in the scalp fetal ECG. The association is quantified as the coherence between the processed data and the gold standard. The maximum coherence values calculated for each approach were compared using the paired t-test. Our results showed no difference in the accuracy between the frequency and time domain approach (p = 0.733). However, the association was higher between the frequency domain data and the gold standard compared to the template subtraction data and the gold standard (p = 0.049), indicating that the frequency domain approach yielded a signal that resembled that of the scalp ECG compared to the time domain approach.

The search for new therapies to reduce symptoms and find a cure for Parkinson's disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson's disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease.