Differential T cell accumulation within intracranial and subcutaneous melanomas is associated with differences in intratumoral myeloid cells.

Patients with metastatic brain melanomas (MBM) experience shorter-lasting survival than patients with extracranial metastases, and this is associated with a higher fraction of dysfunctional CD8 T cells. The goal of this study was to understand the underlying cause of T cell dysfunction in MBM. To accomplish this, we compared murine B16 melanomas implanted intracranially (IC) or subcutaneously (SC).

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

Background And Objectives: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH.

CARD9 attenuates Aβ pathology and modifies microglial responses in an Alzheimer's disease mouse model.

Recent advances have highlighted the importance of several innate immune receptors expressed by microglia in Alzheimer's disease (AD). In particular, mounting evidence from AD patients and experimental models indicates pivotal roles for TREM2, CD33, and CD22 in neurodegenerative disease progression. While there is growing interest in targeting these microglial receptors to treat AD, we still lack knowledge of the downstream signaling molecules used by these receptors to orchestrate immune responses in AD.

The meningeal transcriptional response to traumatic brain injury and aging.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury.

SYK coordinates neuroprotective microglial responses in neurodegenerative disease.

Recent studies have begun to reveal critical roles for the brain's professional phagocytes, microglia, and their receptors in the control of neurotoxic amyloid beta (Aβ) and myelin debris accumulation in neurodegenerative disease. However, the critical intracellular molecules that orchestrate neuroprotective functions of microglia remain poorly understood. In our studies, we find that targeted deletion of SYK in microglia leads to exacerbated Aβ deposition, aggravated neuropathology, and cognitive defects in the 5xFAD mouse model of Alzheimer's disease (AD).

Neuroimmune cleanup crews in brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability. Mounting evidence indicates that the immune system is critically involved in TBI pathogenesis, where it is deployed to dispose of neurotoxic material generated from head trauma and to instruct the wound healing process. However, the immune response to brain damage must be carefully held in check as aberrant regulation of immune signaling can lead to deleterious neuroinflammation, brain pathology, and neurological dysfunction.

Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.

Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics.

AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment.

Neurodevelopment is characterized by rapid rates of neural cell proliferation and differentiation followed by massive cell death in which more than half of all recently generated brain cells are pruned back. Large amounts of DNA damage, cellular debris, and by-products of cellular stress are generated during these neurodevelopmental events, all of which can potentially activate immune signalling. How the immune response to this collateral damage influences brain maturation and function remains unknown.

Crosstalk Between the Microbiome and Gestational Immunity in Autism-Related Disorders.

The etiologies of most neurodevelopmental disorders, including autism spectrum disorder (ASD), remain incompletely understood. However, recent epidemiological and experimental data suggest that dysregulated maternal immune activation (MIA) can impede normal brain maturation and promote the development of autism-related phenotypes. Indeed, our studies and work by others demonstrate that offspring born to pregnant animals that were exposed to immune activators develop many of the defining behavioral features of ASD, including abnormalities in social preference, communicative impairments, and repetitive/stereotyped behaviors.

Th17 Cells in Parkinson's Disease: The Bane of the Midbrain.

Emerging data implicate potential roles for T cells in Parkinson's disease (PD); however, direct evidence for human T cells in PD-associated neurodegeneration has been lacking. In this issue of Cell Stem Cell, Sommer et al. (2018) demonstrate that IL-17-producing T cells from sporadic PD patients promote cell death of patient iPSC-derived midbrain neurons.

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism.

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood.