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Mark A. Petersen
University of California, San Francisco
10Publications
8H-index
581Citations
Publications 10
Newest
#1Katerina AkassoglouH-Index: 45
Last.Mark A. PetersenH-Index: 8
view all 3 authors...
Source
#1Jae K. Ryu (Gladstone Institutes)H-Index: 36
#2Victoria A. Rafalski (Gladstone Institutes)H-Index: 11
Last.Katerina Akassoglou (UCSD: University of California, San Diego)H-Index: 45
view all 35 authors...
Activation of innate immunity and deposition of blood-derived fibrin in the central nervous system (CNS) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis (MS) and Alzheimer’s disease (AD). However, the mechanisms that link disruption of the blood–brain barrier (BBB) to neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody...
19 CitationsSource
#1Nathanael J. Lee (NIH: National Institutes of Health)H-Index: 2
#2Seung-Kwon Ha (NIH: National Institutes of Health)H-Index: 3
Last.Daniel S. Reich (NIH: National Institutes of Health)H-Index: 48
view all 14 authors...
13 CitationsSource
#1Mark A. PetersenH-Index: 8
#2Jae K. RyuH-Index: 36
Last.Katerina AkassoglouH-Index: 45
view all 3 authors...
Fibrinogen enters the brain in a wide range of brain diseases that involve blood–brain barrier disruption. In this Review, Petersen et al. discuss recent evidence that fibrinogen causes damage that contributes to the pathology of a range of neurological disorders and discuss therapeutic implications.
40 CitationsSource
#1Mark A. Petersen (UCSF: University of California, San Francisco)H-Index: 8
#2Jae K. Ryu (Gladstone Institutes)H-Index: 36
Last.Katerina Akassoglou (UCSF: University of California, San Francisco)H-Index: 45
view all 28 authors...
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiati...
28 CitationsSource
#1Jae K. Ryu (UCSF: University of California, San Francisco)H-Index: 36
#2Mark A. Petersen (UCSF: University of California, San Francisco)H-Index: 8
Last.Katerina Akassoglou (UCSF: University of California, San Francisco)H-Index: 45
view all 16 authors...
Autoimmunity and macrophage recruitment into the central nervous system (CNS) are critical determinants of neuroinflammatory diseases. However, the mechanisms that drive immunological responses targeted to the CNS remain largely unknown. Here we show that fibrinogen, a central blood coagulation protein deposited in the CNS after blood–brain barrier disruption, induces encephalitogenic adaptive immune responses and peripheral macrophage recruitment into the CNS leading to demyelination. Fibrinoge...
94 CitationsSource
#1Dimitrios Davalos (UCSF: University of California, San Francisco)H-Index: 17
#2Kim M. Baeten (UCSF: University of California, San Francisco)H-Index: 5
Last.Katerina Akassoglou (UCSF: University of California, San Francisco)H-Index: 45
view all 13 authors...
Although multiple sclerosis (MS) has been associated with the coagulation system, the temporal and spatial regulation of coagulation activity in neuroinflammatory lesions is unknown. Using a novel molecular probe, we characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded onset of neurological signs, increased at disease peak, and correlated with fibrin deposition, microglial activat...
51 CitationsSource
#1Jae K. Ryu (UCSF: University of California, San Francisco)H-Index: 36
#2Kim M. Baeten (UCSF: University of California, San Francisco)H-Index: 5
Last.Katerina Akassoglou (UCSF: University of California, San Francisco)H-Index: 45
view all 13 authors...
Blood–brain barrier (BBB) disruption, which allows the leakage and deposition of plasma proteins in the central nervous system (CNS), is a hallmark of multiple sclerosis (MS), a chronic autoimmune disease of the CNS characterized by activation of innate and adaptive immune responses. However, the contribution of increased vascular permeability to the development of autoimmunity remains unclear. Here we show that the plasma protein fibrinogen, the physiological ligand of complement receptor 3 (CR...
Source
#1Dimitrios Davalos (UCSF: University of California, San Francisco)H-Index: 17
#2Jae K. Ryu (UCSF: University of California, San Francisco)H-Index: 36
Last.Katerina Akassoglou (UCSF: University of California, San Francisco)H-Index: 45
view all 16 authors...
Multiple sclerosis is characterized by the activation of microglia cells. Davalos et al. investigate the early stages of neuroinflammation in mice and reveal that the plasma protein fibrinogen induces microglial clustering around the brain vasculature, which facilitates lesion formation and focal axonal damage.
226 CitationsSource
#1Mark A. Petersen (UI: University of Iowa)H-Index: 8
#2Michael E. Dailey (UI: University of Iowa)H-Index: 27
We used two-channel three-dimensional time-lapse fluorescence confo- cal imaging in live rat hippocampal slice cultures (1-7 days in vitro) to determine the motility behaviors of activated microglia as they engage dead and dying cells following traumatic brain tissue injury. Live microglia were labeled with a fluorescently conju- gated lectin (IB4), and dead neurons were labeled with a membrane-impermeant fluo- rescent DNA-binding dye (Sytox Orange or To-Pro-3). Tissue injury during the slicing ...
110 CitationsSource
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