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Anthony J Filiano

Assistant Professor in Neurosurgery
Neurosurgery
DUMC 3350, Durham, NC 27710
701 W. Main St, Chesterfield Bldg Room 5424, Durham, NC 27701

Selected Publications


Mural cells interact with macrophages in the dura mater to regulate CNS immune surveillance.

Journal Article J Exp Med · February 5, 2024 The central nervous system (CNS) tightly regulates access of circulating immune cells. Immunosurveillance is therefore managed in the meninges at the borders of the CNS. Here, we demonstrated that mural cells, which include pericytes and smooth muscle cell ... Full text Link to item Cite

Mesenchymal stromal cells suppress microglial activation and tumor necrosis factor production.

Journal Article Cytotherapy · February 2024 BACKGROUND AIMS: White matter diseases are commonly associated with microglial activation and neuroinflammation. Mesenchymal stromal cells (MSCs) have immunomodulatory properties and thus have the potential to be developed as cell therapy for white matter ... Full text Link to item Cite

Prolonged STAT1 activation in neurons drives a pathological transcriptional response.

Journal Article J Neuroimmunol · September 15, 2023 Neurons require physiological IFN-γ signaling to maintain central nervous system (CNS) homeostasis, however, pathological IFN-γ signaling can cause CNS pathologies. The downstream signaling mechanisms that cause these drastically different outcomes in neur ... Full text Link to item Cite

An International Society for Cell and Gene Therapy Mesenchymal Stromal Cells (MSC) Committee perspectives on International Standards Organization/Technical Committee 276 Biobanking Standards for bone marrow-MSCs and umbilical cord tissue-derived MSCs for research purposes.

Journal Article Cytotherapy · August 2023 The rapidly growing field of mesenchymal stromal cell (MSC) basic and translational research requires standardization of terminology and functional characterization. The International Standards Organization's (ISO) Technical Committee (TC) on Biotechnology ... Full text Link to item Cite

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

Journal Article Br J Anaesth · February 2023 BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Her ... Full text Link to item Cite

Improving thymus implantation for congenital athymia with interleukin-7.

Journal Article Clin Transl Immunology · 2023 OBJECTIVES: Thymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus im ... Full text Open Access Link to item Cite

Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model.

Journal Article Cureus · December 2022 INTRODUCTION: Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins ... Full text Link to item Cite

Unique aspects of IFN-γ/STAT1 signaling in neurons.

Journal Article Immunol Rev · October 2022 The IFN-γ/STAT1 immune signaling pathway impacts many homeostatic and pathological aspects of neurons, beyond its canonical role in controlling intracellular pathogens. Well known for its potent pro-inflammatory and anti-viral functions in the periphery, t ... Full text Link to item Cite

ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

Journal Article The Journal of clinical investigation · April 2021 Full text Cite

Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies.

Journal Article Stem Cells · January 2021 Mesenchymal stromal cells (MSCs) are widely used in clinical trials because of their ability to modulate inflammation. The success of MSCs has been variable over 25 years, most likely due to an incomplete understanding of their mechanism. After MSCs are in ... Full text Open Access Link to item Cite

Mural cells interact with macrophages in the dura mater to regulate CNS immune surveillance.

Journal Article J Exp Med · February 5, 2024 The central nervous system (CNS) tightly regulates access of circulating immune cells. Immunosurveillance is therefore managed in the meninges at the borders of the CNS. Here, we demonstrated that mural cells, which include pericytes and smooth muscle cell ... Full text Link to item Cite

Mesenchymal stromal cells suppress microglial activation and tumor necrosis factor production.

Journal Article Cytotherapy · February 2024 BACKGROUND AIMS: White matter diseases are commonly associated with microglial activation and neuroinflammation. Mesenchymal stromal cells (MSCs) have immunomodulatory properties and thus have the potential to be developed as cell therapy for white matter ... Full text Link to item Cite

Prolonged STAT1 activation in neurons drives a pathological transcriptional response.

Journal Article J Neuroimmunol · September 15, 2023 Neurons require physiological IFN-γ signaling to maintain central nervous system (CNS) homeostasis, however, pathological IFN-γ signaling can cause CNS pathologies. The downstream signaling mechanisms that cause these drastically different outcomes in neur ... Full text Link to item Cite

An International Society for Cell and Gene Therapy Mesenchymal Stromal Cells (MSC) Committee perspectives on International Standards Organization/Technical Committee 276 Biobanking Standards for bone marrow-MSCs and umbilical cord tissue-derived MSCs for research purposes.

Journal Article Cytotherapy · August 2023 The rapidly growing field of mesenchymal stromal cell (MSC) basic and translational research requires standardization of terminology and functional characterization. The International Standards Organization's (ISO) Technical Committee (TC) on Biotechnology ... Full text Link to item Cite

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

Journal Article Br J Anaesth · February 2023 BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Her ... Full text Link to item Cite

Improving thymus implantation for congenital athymia with interleukin-7.

Journal Article Clin Transl Immunology · 2023 OBJECTIVES: Thymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus im ... Full text Open Access Link to item Cite

Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model.

Journal Article Cureus · December 2022 INTRODUCTION: Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins ... Full text Link to item Cite

Unique aspects of IFN-γ/STAT1 signaling in neurons.

Journal Article Immunol Rev · October 2022 The IFN-γ/STAT1 immune signaling pathway impacts many homeostatic and pathological aspects of neurons, beyond its canonical role in controlling intracellular pathogens. Well known for its potent pro-inflammatory and anti-viral functions in the periphery, t ... Full text Link to item Cite

ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

Journal Article The Journal of clinical investigation · April 2021 Full text Cite

Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies.

Journal Article Stem Cells · January 2021 Mesenchymal stromal cells (MSCs) are widely used in clinical trials because of their ability to modulate inflammation. The success of MSCs has been variable over 25 years, most likely due to an incomplete understanding of their mechanism. After MSCs are in ... Full text Open Access Link to item Cite

Risk of epilepsy in rheumatoid arthritis: a meta-analysis of population based studies and bioinformatics analysis.

Journal Article Ther Adv Chronic Dis · 2020 BACKGROUND: An increasing number of studies support an association between rheumatoid arthritis (RA) and brain disorders. This study aims to determine the association between RA and epilepsy. METHODS: A comprehensive search of databases in both English and ... Full text Link to item Cite

Updating Neuroimmune Targets in Central Nervous System Dysfunction.

Journal Article Trends Pharmacol Sci · July 2019 Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain b ... Full text Link to item Cite

Reduction of microglial progranulin does not exacerbate pathology or behavioral deficits in neuronal progranulin-insufficient mice.

Journal Article Neurobiol Dis · April 2019 Loss-of-function mutations in progranulin (GRN), most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Individuals with loss-of-function mutations on both GRN alleles develop neuronal cer ... Full text Link to item Cite

Human umbilical cord blood monocytes, but not adult blood monocytes, rescue brain cells from hypoxic-ischemic injury: Mechanistic and therapeutic implications.

Journal Article PLoS One · 2019 Cord blood (CB) mononuclear cells (MNC) are being tested in clinical trials to treat hypoxic-ischemic (HI) brain injuries. Although early results are encouraging, mechanisms underlying potential clinical benefits are not well understood. To explore these m ... Full text Open Access Link to item Cite

Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury.

Journal Article J Exp Med · July 2, 2018 Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cell ... Full text Link to item Cite

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.

Journal Article J Exp Med · June 4, 2018 Featured Publication Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essen ... Full text Link to item Cite

Meningeal whole mount preparation and characterization of neural cells by flow cytometry.

Journal Article Curr Protoc Immunol · April 2018 Neuroimmunologists aim to understand the interactions between the central nervous system and the immune system under both homeostatic and pathological conditions. The meninges, contrary to the brain parenchyma, are populated by numerous immune cells. Solub ... Full text Link to item Cite

Myeloid Cells in the Central Nervous System.

Journal Article Immunity · June 20, 2017 The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages, as well as choroid plexus and meningeal macrophages, dendritic cells, and granulocytes. ... Full text Link to item Cite

How and why do T cells and their derived cytokines affect the injured and healthy brain?

Journal Article Nat Rev Neurosci · June 2017 The evolution of adaptive immunity provides enhanced defence against specific pathogens, as well as homeostatic immune surveillance of all tissues. Despite being 'immune privileged', the CNS uses the assistance of the immune system in physiological and pat ... Full text Link to item Cite

Restoring neuronal progranulin reverses deficits in a mouse model of frontotemporal dementia.

Journal Article Brain · May 1, 2017 Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotio ... Full text Link to item Cite

Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour.

Journal Article Nature · July 21, 2016 Featured Publication Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing beh ... Full text Link to item Cite

Progranulin haploinsufficiency causes biphasic social dominance abnormalities in the tube test.

Journal Article Genes Brain Behav · July 2016 Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia (FTD), a neurodegenerative disorder in which social behavior is disrupted. Progranulin-insufficient mice, both Grn(+/-) and Grn(-/-) , are used ... Full text Link to item Cite

Interactions of innate and adaptive immunity in brain development and function.

Journal Article Brain Res · August 18, 2015 It has been known for decades that the immune system has a tremendous impact on behavior. Most work has described the negative role of immune cells on the central nervous system. However, we and others have demonstrated over the last decade that a well-reg ... Full text Link to item Cite

Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD.

Journal Article J Exp Med · September 22, 2014 Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gen ... Full text Link to item Cite

ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

Journal Article J Clin Invest · March 2014 Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS m ... Full text Link to item Cite

Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice.

Journal Article J Neurosci · March 20, 2013 Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations in GRN, the progranulin gene, are a common genetic cause of the disorder, but the mechanisms by wh ... Full text Link to item Cite

The application of permanent middle cerebral artery ligation in the mouse.

Journal Article Journal of visualized experiments : JoVE · December 1, 2011 Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques ... Cite

The application of permanent middle cerebral artery ligation in the mouse.

Journal Article J Vis Exp · July 25, 2011 Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques ... Full text Link to item Cite

Transglutaminase 2 protects against ischemic stroke.

Journal Article Neurobiol Dis · September 2010 Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible facto ... Full text Link to item Cite

Transglutaminase 2 protects against ischemic insult, interacts with HIF1beta, and attenuates HIF1 signaling.

Journal Article FASEB J · August 2008 Transglutaminase 2 (TG2) is a multifunctional enzyme that has been implicated in the pathogenesis of neurodegenerative diseases, ischemia, and stroke. The mechanism by which TG2 modulates disease progression have not been elucidated. In this study we inves ... Full text Link to item Cite

Glutamate decreases mitochondrial size and movement in primary forebrain neurons.

Journal Article J Neurosci · August 27, 2003 Mitochondria are essential to maintain neuronal viability. In addition to the generation of ATP and maintenance of calcium homeostasis, the effective delivery of mitochondria to the appropriate location within neurons is also likely to influence their func ... Full text Link to item Cite

Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation.

Journal Article J Cereb Blood Flow Metab · July 2002 Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes ... Full text Link to item Cite