Early detection of thrombin activity in neuroinflammatory disease

被引：84

作者：

Davalos, Dimitrios ^{[1
]}

Baeten, Kim M. ^{[1
]}

Whitney, Michael A. ^{[2
]}

Mullins, Eric S. ^{[3
]}

Friedman, Beth ^{[2
]}

Olson, Emilia S. ^{[2
]}

Ryu, Jae Kyu ^{[1
]}

Smirnoff, Dimitri S. ^{[1
]}

Petersen, Mark A. ^{[1
,4
]}

Bedard, Catherine ^{[1
]}

Degen, Jay L. ^{[3
]}

Tsien, Roger Y. ^{[2
,5
,6
]}

Akassoglou, Katerina ^{[1
,7
]}

机构：

[1] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA

[2] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[3] Univ Cincinnati, Coll Med, Canc & Blood Dis Inst, Div Expt Hematol, Cincinnati, OH USA

[4] Univ Calif San Francisco, Dept Pediat, Div Neonatol, San Francisco, CA 94158 USA

[5] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Howard Hughes Med Inst, San Diego, CA 92103 USA

[7] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

来源：

ANNALS OF NEUROLOGY | 2014年 / 75卷 / 02期

关键词：

CELL-PENETRATING PEPTIDES; BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS LESIONS; IN-VIVO; DAMAGE; FLUORESCENCE; PROTHROMBIN; ACTIVATION;

D O I：

10.1002/ana.24078

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Thrombin activity might be exploited for developing sensitive probes for preclinical detection and monitoring of neuroinflammation and MS progression. Ann Neurol 2014;75:303-308

引用

页码：303 / 308

页数：6

共 25 条

[1] Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: Lessons from multiple sclerosis [J].

Adams, R. A. ;

Schachtrup, C. ;

Davalos, D. ;

Tsigelny, I. ;

Akassoglou, K. .

CURRENT MEDICINAL CHEMISTRY, 2007, 14 (27) :2925-2936

[2] The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease [J].

Adams, Ryan A. ;

Bauer, Jan ;

Flick, Matthew J. ;

Sikorski, Shoana L. ;

Nuriel, Tal ;

Lassmann, Hans ;

Degen, Jay L. ;

Akassoglou, Katerina .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (03) :571-582

[3] Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain [J].

Arai, T ;

Miklossy, J ;

Klegeris, A ;

Guo, JP ;

McGeer, PL .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2006, 65 (01) :19-25

[4] Thrombin and platelet activation [J].

Brass, LF .

CHEST, 2003, 124 (03) :18S-25S

[5] Thrombin Activity Associated with Neuronal Damage during Acute Focal Ischemia [J].

Chen, Bo ;

Friedman, Beth ;

Whitney, Michael A. ;

Van Winkle, Jessica A. ;

Lei, I-Farn ;

Olson, Emilia S. ;

Cheng, Qun ;

Pereira, Benedict ;

Zhao, Lifu ;

Tsien, Roger Y. ;

Lyden, Patrick D. .

JOURNAL OF NEUROSCIENCE, 2012, 32 (22) :7622-7631

[6] Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation [J].

Davalos, Dimitrios ;

Ryu, Jae Kyu ;

Merlini, Mario ;

Baeten, Kim M. ;

Le Moan, Natacha ;

Petersen, Mark A. ;

Deerinck, Thomas J. ;

Smirnoff, Dimitri S. ;

Bedard, Catherine ;

Hakozaki, Hiroyuki ;

Murray, Sara Gonias ;

Ling, Jennie B. ;

Lassmann, Hans ;

Degen, Jay L. ;

Ellisman, Mark H. ;

Akassoglou, Katerina .

NATURE COMMUNICATIONS, 2012, 3

[7] Fibrinogen as a key regulator of inflammation in disease [J].

Davalos, Dimitrios ;

Akassoglou, Katerina .

SEMINARS IN IMMUNOPATHOLOGY, 2012, 34 (01) :43-62

[8] BLOOD-BRAIN-BARRIER DAMAGE IN ACUTE MULTIPLE-SCLEROSIS PLAQUES - AN IMMUNOCYTOLOGICAL STUDY [J].

GAY, D ;

ESIRI, M .

BRAIN, 1991, 114 :557-572

[9] Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets [J].

Han, May H. ;

Hwang, Sun-Il ;

Roy, Dolly B. ;

Lundgren, Deborah H. ;

Price, Jordan V. ;

Ousman, Shalina S. ;

Fernald, Guy Haskin ;

Gerlitz, Bruce ;

Robinson, William H. ;

Baranzini, Sergio E. ;

Grinnell, Brian W. ;

Raine, Cedric S. ;

Sobel, Raymond A. ;

Han, David K. ;

Steinman, Lawrence .

NATURE, 2008, 451 (7182) :1076-U2

[10] Multiple Sclerosis: Prospects and Promise [J].

Hauser, Stephen L. ;

Chan, Jonah R. ;

Oksenberg, Jorge R. .

ANNALS OF NEUROLOGY, 2013, 74 (03) :317-327

← 1 2 3 →