'The molecular basis of mechanosensory transduction by primary sensory neurones remains poorly understood. Amongst candidate transducer molecules are members of the acid-sensing ion channel (ASIC) family; nerve fibre recordings have shown ASIC2 and ASIC3 null mutants have aberrant responses to suprathreshold mechanical stimuli. Using the neuronal cell body as a ... More
'To delineate the roles that oxygen and fibroblast growth factors (FGFs) play in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture ... More
MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation.
AuthorsFricker M, Neher JJ, Zhao JW, Théry C, Tolkovsky AM, Brown GC,
JournalJ Neurosci
PubMed ID22357850
'Milk-fat globule EGF factor-8 (MFG-E8, SED1, lactadherin) is known to mediate the phagocytic removal of apoptotic cells by bridging phosphatidylserine (PS)-exposing cells and the vitronectin receptor (VR) on phagocytes. However, we show here that MFG-E8 can mediate phagocytosis of viable neurons during neuroinflammation induced by lipopolysaccharide (LPS), thereby causing neuronal ... More
Lectin mapping reveals stage-specific display of surface carbohydrates in in vitro and haemolymph-derived cells of the entomopathogenic fungus Beauveria bassiana.
AuthorsWanchoo A, Lewis MW, Keyhani NO,
JournalMicrobiology
PubMed ID19608611
'The entomopathogenic fungus Beauveria bassiana and its insect host target represent a model system with which to examine host-pathogen interactions. Carbohydrate epitopes on the surfaces of fungal cells play diverse roles in processes that include adhesion, non-self recognition and immune invasion with respect to invertebrate hosts. B. bassiana produces a ... More
Early activation, motility, and homing of neonatal microglia to injured neurons does not require protein synthesis.
AuthorsKurpius D, Wilson N, Fuller L, Hoffman A, Dailey ME
JournalGlia
PubMed ID16715500
'Neuronal injury in CNS tissues induces a rapid activation and mobilization of resident microglia (MG). It is widely assumed that changes in gene expression drive the morphological transformation of MG and regulate their mobilization during activation. Here, we used acutely excised neonatal rat brain slices to test whether the morphological ... More
Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia.
AuthorsFricker M, Vilalta A, Tolkovsky AM, Brown GC,
JournalJ Biol Chem
PubMed ID23386613
'Microglia are resident brain macrophages, which can cause neuronal loss when activated in infectious, ischemic, traumatic, and neurodegenerative diseases. Caspase-8 has both prodeath and prosurvival roles, mediating apoptosis and/or preventing RIPK1-mediated necroptosis depending on cell type and stimulus. We found that inflammatory stimuli (LPS, lipoteichoic acid, or TNF-a) caused an ... More
Isolectin-IB 4 as a vascular stain for the study of adult neurogenesis.
AuthorsErnst C, Christie BR
JournalJ Neurosci Methods
PubMed ID16095716
'It has been proposed that new neurons in the adult brain might preferentially develop in the immediate vicinity of existing vasculature, an area that has been referred to as a "vascular niche". The most common method for identifying neurons that arise as the result of mitotic activity is to label ... More
In vivo visualization and functional characterization of primary somatic neurons.
AuthorsMa C, Donnelly DF, LaMotte RH,
JournalJ Neurosci Methods
PubMed ID20558205
In vivo electrophysiological recordings from cell bodies of primary sensory neurons are used to determine sensory function but are commonly performed blindly and without access to voltage- (patch-clamp) electrophysiology or optical imaging. We present a procedure to visualize and patch-clamp the neuronal cell body in the dorsal root ganglion, in ... More
Opioid-related (ORL1) receptors are enriched in a subpopulation of sensory neurons and prolonged activation produces no functional loss of surface N-type calcium channels.
The opioid-related receptor, ORL1, is activated by the neuropeptide nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage-activated (HVA) calcium channel currents (I(Ca)) via a G-protein-coupled mechanism. Endocytosis of ORL1 receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage-gated calcium channel (VGCC) internalization via physical interaction between ORL1 and the N-type ... More
Combinatorial expression of Brn3 transcription factors in somatosensory neurons: genetic and morphologic analysis.
AuthorsBadea TC, Williams J, Smallwood P, Shi M, Motajo O, Nathans J,
JournalJ Neurosci
PubMed ID22262898
The three members of the Brn3 family of POU-domain transcription factors (Brn3a/Pou4f1, Brn3b/Pou4f2, and Brn3c/Pou4f3) are expressed in overlapping subsets of visual, auditory/vestibular, and somatosensory neurons. Using unmarked Brn3-null alleles and Brn3 conditional alleles in which gene loss is coupled to expression of an alkaline phosphatase reporter, together with sparse ... More
Long-term IL-1ß exposure causes subpopulation-dependent alterations in rat dorsal root ganglion neuron excitability.
AuthorsStemkowski PL, Smith PA,
JournalJ Neurophysiol
PubMed ID22170966
The effect of interleukin-1ß (IL-1ß) on the electrical properties of sensory neurons was assessed at levels and exposure times comparable to those found in animal models of neuropathic pain. Experiments involved whole cell current-clamp recordings from rat dorsal root ganglion (DRG) neurons in defined-medium, neuron-enriched cultures. Five- to six-day exposure ... More
Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats.
AuthorsTu H, Liu J, Zhu Z, Zhang L, Pipinos II, Li YL,
JournalJ Neurophysiol
PubMed ID22072507
Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage-gated sodium (Na(v)) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in the CHF state. The present study examined the role of mitochondria-derived ... More
A new method to isolate microglia from adult mice and culture them for an extended period of time.
AuthorsMoussaud S, Draheim HJ,
JournalJ Neurosci Methods
PubMed ID20097228
As the major immuno-competent cells of the brain, microglia are highly implicated in neuro-protection as well as in neurodegeneration. Therefore, they are of key interest for research on numerous CNS diseases. Currently, to model inflammation in the brain, microglial cell lines or primary microglia prepared from embryonic or neo-natal rodents ... More
Microglial cells in astroglial cultures: a cautionary note.
AuthorsSaura J,
JournalJ Neuroinflammation
PubMed ID17937799
Primary rodent astroglial-enriched cultures are the most popular model to study astroglial biology in vitro. From the original methods described in the 1970's a great number of minor modifications have been incorporated into these protocols by different laboratories. These protocols result in cultures in which the astrocyte is the predominant ... More
Microvessel formation from mouse embryonic aortic explants is oxygen and VEGF dependent.
AuthorsAkimoto T, Liapis H, Hammerman MR
JournalAm J Physiol Regul Integr Comp Physiol
PubMed ID12121862
To delineate the roles of O(2) and vascular endothelial growth factor (VEGF) in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture ... More
Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways.
AuthorsDi Castro A, Drew LJ, Wood JN, Cesare P
JournalProc Natl Acad Sci U S A
PubMed ID16537426
Many sensations of pain are evoked by mechanical stimuli, and in inflammatory conditions, sensitivity to such stimuli is commonly increased. Here we used cultured sensory neurons as a model of the peripheral terminal to investigate the effects of inflammatory signaling pathways on mechanosensitive ion channels. Activation of two of these ... More
Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway.
Innate immunity is an evolutionarily ancient system that provides organisms with immediately available defense mechanisms through recognition of pathogen-associated molecular patterns. We show that in the CNS, specific activation of innate immunity through a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration. We identify microglia as the major lipopolysaccharide (LPS)-responsive ... More
MEGF9: a novel transmembrane protein with a strong and developmentally regulated expression in the nervous system.
AuthorsBrandt-Bohne U, Keene DR, White FA, Koch M
JournalBiochem J
PubMed ID16981854
MEGF9 [multiple EGF (epidermal growth factor)-like-domains 9], a novel transmembrane protein with multiple EGF-like repeats, is predominantly expressed in the developing and adult CNS (central nervous system) and PNS (peripheral nervous system). The domain structure of MEGF9 consists of an N-terminal region with several potential O-glycosylation sites followed by five ... More
Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase.
AuthorsMander PK, Jekabsone A, Brown GC
JournalJ Immunol
PubMed ID16393992
Microglia are resident brain macrophages that become activated and proliferate following brain damage or stimulation by immune mediators, such as IL-1beta or TNF-alpha. We investigated the mechanisms by which microglial proliferation is regulated in primary cultures of rat glia. We found that basal proliferation of microglia was stimulated by proinflammatory ... More
Bidirectional control of CNS capillary diameter by pericytes.
AuthorsPeppiatt CM, Howarth C, Mobbs P, Attwell D
JournalNature
PubMed ID17036005
Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation ... More
Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid.
AuthorsMême W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C
JournalFASEB J
PubMed ID16423877
Brain inflammation is characterized by a reactive gliosis involving the activation of astrocytes and microglia. This process, common to many brain injuries and diseases, underlies important phenotypic changes in these two glial cell types. One characteristic feature of astrocytes is their high level of intercellular communication mediated by gap junctions. ... More
Regulation of angiogenesis by vascular endothelial growth factor and angiopoietin-1 in the rat aorta model: distinct temporal patterns of intracellular signaling correlate with induction of angiogenic sprouting.
AuthorsZhu WH, MacIntyre A, Nicosia RF
JournalAm J Pathol
PubMed ID12213710
Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) promote the spontaneous angiogenic response of freshly cut rat aortic rings. When VEGF and Ang-1 were tested in cultures of 14-day-old rings, which are quiescent and unable to spontaneously produce neovessels, only VEGF was capable of inducing an angiogenic response. Ang-1 failed ... More
Migration of perilesional microglia after focal brain injury and modulation by CC chemokine receptor 5: an in situ time-lapse confocal imaging study.
AuthorsCarbonell WS, Murase S, Horwitz AF, Mandell JW
JournalJ Neurosci
PubMed ID16049180
Microglia rapidly become reactive in response to diverse stimuli and are thought to be prominent participants in the pathophysiology of both acute injury and chronic neurological diseases. However, mature microglial reactions to a focal lesion have not been characterized dynamically in adult vertebrate tissue. Here, we present a detailed analysis ... More
The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS.
The immediate or innate immune response is the first line of defense against diverse microbial pathogens and requires the expression of recently discovered toll-like receptors (TLRs). TLR4 serves as a specific receptor for lipopolysaccharide (LPS) and is localized on the surface of a subset of mammalian cells. Although innate immunity ... More
Mfsd2a is critical for the formation and function of the blood-brain barrier.
Authors
JournalNature
PubMed ID24828040
Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability.
Authors
JournalNat Mater
PubMed ID28783156
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.
Authors
JournalCancer Cell
PubMed ID28870739
Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade.
Authors
JournalNat Med
PubMed ID26479925
An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
AuthorsGoveia J, Rohlenova K, Taverna F, Treps L, Conradi LC, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, García-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwé H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thi
JournalCancer Cell
PubMed ID32183954
Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization.
Authors
JournalNat Med
PubMed ID25894826
An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
Authors
JournalCancer Cell
PubMed ID31935371
A craniofacial-specific monosynaptic circuit enables heightened affective pain.
Authors
JournalNat Neurosci
PubMed ID29184209
STING controls nociception via type I interferon signalling in sensory neurons.
Authors
JournalNature
PubMed ID33442058
Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders.
Authors
JournalNat Cell Biol
PubMed ID35550612
DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity.
Authors
JournalCell Metab
PubMed ID22883231
Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis.
AuthorsDiebold LP, Gil HJ, Gao P, Martinez CA, Weinberg SE, Chandel NS
JournalNat Metab
PubMed ID31106291
Endothelial cells (ECs) require glycolysis for proliferation and migration during angiogenesis; however, the necessity for the mitochondrial respiratory chain during angiogenesis is not known. Here we report that inhibition of respiratory chain complex III impairs proliferation, but not migration of ECs ... More
Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke.
AuthorsLadwig A, Rogall R, Hucklenbroich J, Willuweit A, Schoeneck M, Langen KJ, Fink GR, Rueger MA, Schroeter M
JournalJ Neuroimmune Pharmacol
PubMed ID30488353
Cortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. ... More
Single-Cell RNA Sequencing Maps Endothelial Metabolic Plasticity in Pathological Angiogenesis.
AuthorsRohlenova K, Goveia J, García-Caballero M, Subramanian A, Kalucka J, Treps L, Falkenberg KD, de Rooij LPMH, Zheng Y, Lin L, Sokol L, Teuwen LA, Geldhof V, Taverna F, Pircher A, Conradi LC, Khan S, Stegen S, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Vinckier S, Van Bergen T, Ectors N, De Haes P, Wang J, Bolund L, Schoonjans L, Karakach TK, Yang H, Carmeliet G, Liu Y, Thienpont B, Dewerchin M, Eelen G, Li X, Luo Y, Carmeliet P
JournalCell Metab
PubMed ID32268117
Endothelial cell (EC) metabolism is an emerging target for anti-angiogenic therapy in tumor angiogenesis and choroidal neovascularization (CNV), but little is known about individual EC metabolic transcriptomes. By single-cell RNA sequencing 28,337 murine choroidal ECs (CECs) and sprouting CNV-ECs, we constructed a taxonomy to characterize their heterogeneity. Comparison with murine ... More
IGFBP-1 in Cardiometabolic Pathophysiology-Insights From Loss-of-Function and Gain-of-Function Studies in Male Mice.
AuthorsHaywood NJ, Slater TA, Drozd M, Warmke N, Matthews C, Cordell PA, Smith J, Rainford J, Cheema H, Maher C, Bridge KI, Yuldasheva NY, Cubbon RM, Kearney MT, Wheatcroft SB
JournalJ Endocr Soc
PubMed ID32190801
We have previously reported that overexpression of human insulin-like growth factor binding protein (IGFBP)-1 in mice leads to vascular insulin sensitization, increased nitric oxide bioavailability, reduced atherosclerosis, and enhanced vascular repair, and in the setting of obesity improves glucose tolerance. Human studies suggest that low levels of IGFBP-1 are permissive ... More
Factors Impacting Efficacy of AAV-Mediated CRISPR-Based Genome Editing for Treatment of Choroidal Neovascularization.
AuthorsChung SH, Mollhoff IN, Nguyen U, Nguyen A, Stucka N, Tieu E, Manna S, Meleppat RK, Zhang P, Nguyen EL, Fong J, Zawadzki R, Yiu G
JournalMol Ther Methods Clin Dev
PubMed ID32128346
Frequent injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a clinical burden for patients with neovascular age-related macular degeneration (AMD). Genomic disruption of