Cell type transcriptional identities are maintained in cultured human brain tissue.

It is becoming more broadly accepted that human-based models are needed to better understand the complexities of the human nervous system and its diseases. The recently developed human brain organotypic culture model is one highly promising model that requires the involvement of neurosurgeons and neurosurgical patients. Studies have investigated the electrophysiological properties of neurons in such human tissues, but the maintenance of other cell types within explanted brain remains largely unknown.

The extreme lateral transodontoid approach for large tumors in children in the ventral craniocervical junction.

Objective: Tumors in the ventral craniocervical junction (CCJ) pose unique challenges, particularly in children. The potential constraints with endoscopic approaches to tumors extending inferiorly and laterally and the risk of CSF leakage can be exacerbated in the pediatric population. Here, the authors present their experience with the extreme lateral transodontoid (ELTO) approach in children with large ventral CCJ tumors as an alternative or complement to anterior approaches.

Immune mechanisms and shared immune targets in neurodegenerative diseases.

The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role.

GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci.

Common AAV gene therapy vectors show indiscriminate transduction of living human brain cell types.

The development of cell-type-specific gene therapy vectors for treating neurological diseases holds great promise, but has relied on animal models with limited translational utility. We have adapted an organotypic model to evaluate adeno-associated virus (AAV) transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons. While there has been significant progress in defining the genetic contributions to ALS, greater than 90 ​% of cases are sporadic, which suggests an environmental component. The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling.

Spatiotemporal Mapping of Auditory Onsets during Speech Production.

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time.

Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state.

T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression.

Hippocampal resection during hemispherotomy: is it needed?

Purpose: Hemispherotomy is an effective surgery for intractable pediatric hemispheric epilepsy. Over the years, the surgical goal has shifted from a complete hemispheric resection (anatomical hemispherectomy) to a disconnective hemispherotomy (DH). Multiple techniques for DH have been described, and often, anterior temporal lobectomy (ATL, with hippocampal resection) is performed.

A survey of the members of the American Society of Pediatric Neurosurgeons and factors associated with well-being.

Objective: The goal of this study was to survey the members of the American Society of Pediatric Neurosurgeons (ASPN) to assess the prevalence and associated risks of burnout among pediatric neurosurgeons. The authors aimed to identify the factors that most significantly contributed to this risk to provide a baseline group of characteristics to improve physician well-being.

Methods: Institutional Review Board approval from the University of Arizona was obtained, and the 7-question and 9-question Mayo Physician Well-Being Index (WBI) was distributed to members of the ASPN (n = 275).

Repeat Exchange Autologous Cranioplasty for Recurrent Benign Osteoma: Meta-analysis and Literature Review.

Osteomas are benign bony lesions that can occur throughout the craniofacial skeleton. Surgical excision can be an effective treatment, as recurrence is relatively uncommon. Outside of incomplete resection, causes of recurrence are poorly documented, especially in the pediatric population.

Meta-analysis identifies common gut microbiota associated with multiple sclerosis.

Background: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies.

Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment.

Subpial resection of epileptogenic tubers: operative nuances and lessons learned.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder. Tubers of the central nervous system are a hallmark of the disorder and often cause epilepsy. Many TSC patients fail to achieve seizure control with medication alone.

National 22-year epilepsy surgery landscape shows increasing open and minimally invasive pediatric epilepsy surgery.

Objectives: A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts.

Methods: In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE).

Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis.

Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules.

The occipital interhemispheric transtentorial approach in infants and toddlers: efficacy and complications.

Introduction: Outcomes for pineal region and superior cerebellar tumors in young children often hinge on extent of microsurgical resection, and thus choosing an approach that provides adequate visualization of pathology is essential. The occipital interhemispheric transtentorial (OITT) approach provides excellent exposure while minimizing cerebellar retraction. However, this approach has not been widely accepted as a viable option for very young children due to concerns for potential blood loss when incising the tentorium.

ApoE ε4-dependent alteration of CXCR3 CD127 CD4 T cells is associated with elevated plasma neurofilament light chain in Alzheimer's disease.

Unlabelled: Recent findings indicate a correlation between the peripheral adaptive immune system and neuroinflammation in Alzheimer's disease (AD). To characterize the composition of adaptive immune cells in the peripheral blood of AD patients, we utilized single-cell mass cytometry (CyTOF) to profile peripheral blood mononuclear cells (PBMCs). Concurrently, we assessed the concentration of proteins associated with AD and neuroinflammation in the plasma of the same subjects.

Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis.

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity.