Remodeling and Characterization Analysis of Corticospinal Tract in Patients with Intracerebral Hemorrhage in the Basal Ganglia.

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6 months.

Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma.

Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.

A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.

An abnormal expansion of a GGGGCC (GC) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the GC repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits.

Rigidity in Parkinson's Disease: The Objective Effect of Levodopa.

Background: Quantitative evidence of levodopa-induced beneficial effects on parkinsonian rigidity in Parkinson's disease (PD) is lacking. Recent research has demonstrated the velocity-dependent nature of objective rigidity in PD and revealed its neural underpinning.

Objective: The present study aimed to examine the effect of levodopa on objective rigidity in PD.

Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit.

Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.

Mitochondrial YME1L1 governs unoccupied protein translocase channels.

Mitochondrial protein import through the outer and inner membranes is key to mitochondrial biogenesis. Recent studies have explored how cells respond when import is impaired by a variety of different insults. Here, we developed a mammalian import blocking system using dihydrofolate reductase fused to the N terminus of the inner membrane protein MIC60.

Diabetes Mellitus Is Not a Risk Factor for Difficult Intubation Among Critically Ill Adults: A Secondary Analysis of Multicenter Trials.

Objectives: Diabetes mellitus has been associated with greater difficulty of tracheal intubation in the operating room. This relationship has not been examined for tracheal intubation of critically ill adults. We examined whether diabetes mellitus was independently associated with the time from induction of anesthesia to intubation of the trachea among critically ill adults.

Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

The association of high-density lipoprotein cargo proteins with brain volume in older adults in the Atherosclerosis Risk in Communities (ARIC).

Background: High-density lipoprotein (HDL) modulates the blood-brain barrier and cerebrovascular integrity, likely influencing the risk of Alzheimer's disease (AD), neurodegeneration, and cognitive decline.

Objective: This study aims to identify HDL protein cargo associated with brain amyloid deposition and brain volume in regions vulnerable to AD pathology in older adults.

Methods: HDL was separated from the plasma of 65 non-demented participants of the Atherosclerosis Risk in Communities (ARIC) study using a fast protein liquid chromatography method.

The potential impact of optimal blood pressure treatment intensity to reduce disparities in dementia between Black and White individuals.

Background: Black adults have higher dementia risk than White adults. Whether tighter population-level blood pressure (BP) control reduces this disparity is unknown.

Objective: Estimate the impact of optimal BP treatment intensity on racial disparities in dementia.

Analyses of Human Genetic Data to Identify Clinically Relevant Domains of Neuroligins.

Neuroligins (NLGNs) are postsynaptic adhesion molecules critical for neuronal development that are highly associated with autism spectrum disorder (ASD). Here, we provide an overview of the literature on rare variants. In addition, we introduce a new approach to analyze human variation within genes to identify sensitive regions that have an increased frequency of ASD-associated variants to better understand NLGN function.

Exosomes in Central Nervous System Diseases: A Comprehensive Review of Emerging Research and Clinical Frontiers.

Exosomes, nano-sized lipid bilayer vesicles, have garnered significant attention as mediators of cell communication, particularly within the central nervous system (CNS). Their unique properties, including high stability, low immunogenicity, and the ability to traverse the blood-brain barrier (BBB), position them as promising tools for understanding and addressing CNS diseases. This comprehensive review delves into the biogenesis, properties, composition, functions, and isolation of exosomes, with a particular focus on their roles in cerebrovascular diseases, neurodegenerative disorders, and CNS tumors.

Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO.

Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes.

12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study.

Background: While semaglutide, approved for type-2 diabetes mellitus (T2DM), is being investigated as a treatment for brain disorders, concerns over adverse neuropsychiatric events have emerged. More data are therefore needed to assess the effects of semaglutide on brain health. This study provides robust estimates of the risk of neurological and psychiatric outcomes following semaglutide use compared to three other antidiabetic medications.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.

Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.

Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available.

Surgical Management of Intracerebral Hemorrhage: New Light on the Horizon?

After 30 years of disappointment, 2 randomized controlled trials investigating the effect of neurosurgical treatment on functional outcome in patients with intracerebral hemorrhage were published in 2024. The ENRICH trial (Early Minimally Invasive Removal of Intracerebral Hemorrhage) studied the efficacy of early minimally invasive hematoma removal in patients with lobar or anterior basal ganglia intracerebral hemorrhage, whereas the SWITCH trial investigated the effect of decompressive craniectomy without hematoma removal in severe deep intracerebral hemorrhage. In this critique article, we will discuss the main findings of these trials, their implications and future perspectives.

Therapeutic reduction of neurocan in murine intracerebral hemorrhage lesions promotes oligodendrogenesis and functional recovery.

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown.

Face pareidolia minimally engages macaque face selective neurons.

The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces.

Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study protocol and rationale.

Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Immunohistochemical labeling of ongoing axonal degeneration 10 days following cervical contusion spinal cord injury in the rat.

Study Design: Experimental Animal Study.

Objective: To continue validating an antibody which targets an epitope of neurofilament light chain (NF-L) only available during neurodegeneration and to utilize the antibody to describe the pattern of axonal degeneration 10 days post-unilateral C4 contusion in the rat.

Setting: University of Florida laboratory in Gainesville, USA.

Building a growing genomic repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).