A5034649449- Neuroinflammation and Neurodegeneration Mechanisms
- Barrier Structure and Function Studies
- Cerebrospinal fluid and hydrocephalus
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Mycobacterium research and diagnosis
- Cytokine Signaling Pathways and Interactions
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Immune Response and Inflammation
- Neonatal and fetal brain pathology
- Caveolin-1 and cellular processes
- Neurological Disease Mechanisms and Treatments
- Spinal Dysraphism and Malformations
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Cell Image Analysis Techniques
- Neonatal Respiratory Health Research
- Fetal and Pediatric Neurological Disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- CAR-T cell therapy research
- Vagus Nerve Stimulation Research
- 3D Printing in Biomedical Research
- Psoriasis: Treatment and Pathogenesis
- Neuroscience and Neural Engineering
Washington University in St. Louis
2021-2025
University of Auckland
2014-2025
Hope Center for Neurological Disorders
2023-2024
Brain Research New Zealand
2016-2022
University of Virginia
2019-2020
Pharmac
2016-2018
The meninges are a membranous structure enveloping the central nervous system (CNS) that host rich repertoire of immune cells mediating CNS surveillance. Here, we report mouse contain pool monocytes and neutrophils supplied not from blood but by adjacent skull vertebral bone marrow. Under pathological conditions, including spinal cord injury neuroinflammation, CNS-infiltrating myeloid can originate brain borders display transcriptional signatures distinct their blood-derived counterparts....
Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near central nervous system (CNS) parenchyma2, their role CNS physiology has not been sufficiently well studied. Given continuous interaction with cerebrospinal fluid (CSF) strategic positioning, we refer to these cells collectively as parenchymal border (PBMs). Here demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation express high levels...
Transforming growth factor beta 1 (TGFβ1) is strongly induced following brain injury and polarises microglia to an anti-inflammatory phenotype. Augmentation of TGFβ1 responses may therefore be beneficial in preventing inflammation neurological disorders including stroke neurodegenerative diseases. However, several other cell types display immunogenic potential identifying the effect on these cells required more fully understand its effects inflammation. Pericytes are multifunctional which...
The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates removal central nervous system (CNS) waste. During aging in Alzheimer’s disease, impaired promotes buildup toxic misfolded proteins CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, mechanisms underlying decline remain elusive. Here, we demonstrate that alterations immunity underlie impairment. Single-cell RNA sequencing...
Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) developing white matter disease-associated (DAMs) prevalent various neurodegenerative conditions. PAMs DAMs share a similar core gene signature. However, the extent of dynamism plasticity these states, as well their functional significance, remains elusive, partly due to lack specific tools. Here, we generated an...
Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events animal models, potential differences human brain versus rodent models makes it imperative that we also study these phenomena cells and tissue. Primary cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, LPS, chemokines IP-10 MCP-1...
Microglia play critical roles in the brain during homeostasis and pathological conditions. Understanding molecular events underpinning microglial functions activation states will further enable us to target these cells for treatment of neurological disorders. The transcription factor PU.1 is development myeloid a major regulator gene expression. In brain, specifically expressed microglia recent evidence from genome-wide association studies suggests that reductions contribute delayed onset...
Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) play an important role in neuroinflammation. To date, majority inflammation-related studies endothelia pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these representative primary human is unclear systematic comparisons inflammatory responses brain-derived has yet to be performed.To study effects neuroinflammation at BBB, brain were isolated from...
Sensory neurons with cell bodies in dorsal root ganglia (DRG) represent a useful model to study axon regeneration. Whereas regeneration and functional recovery occurs after peripheral nerve injury, spinal cord injury or is not followed by regenerative outcomes. Regeneration of sensory axons nerves entirely autonomous. Whether the DRG microenvironment influences different capacities central remains largely unknown. To answer this question, we performed single-cell transcriptional profiling...
Abstract Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-β (PDGFRβ) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment pericyte loss Alzheimer’s disease (AD) well documented. We found that PDGF-BB:PDGFRβ components were altered human AD brains, with marked reduction vascular PDGFB . hypothesised reduced may impact on BBB. therefore tested effects PDGF-BB primary vitro define...
Abstract Microglia, the resident macrophages of central nervous system play vital roles in brain homeostasis through clearance pathogenic material. Microglia are also implicated neurological disorders uncontrolled activation and inflammatory responses. To date, vast majority microglial studies have been performed using rodent models. Human microglia differ from counterparts several aspects including their response to pharmacological substances secretions. Such differences highlight need for...
The meninges membranes surrounding the brain are an immune-blood-brain interface in homeostasis and disease
Abstract Neuroinflammation contributes to the pathogenesis of several neurological disorders and pericytes are implicated in brain inflammatory processes. Cellular responses orchestrated by transcription factors but information on transcriptional control is lacking. Because factor CCAAT/enhancer binding protein delta (C/EBPδ) induced a number disorders, we sought investigate its role regulating pericyte immune responses. Our results reveal that C/EBPδ concentration- time-dependent fashion...