4 research outputs found
Fibrinogen primes the microglial NLRP3 inflammasome and propagates pro-inflammatory signaling via extracellular vesicles: Implications for blood-brain barrier dysfunction
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/02/2023
- Field of study
The brain's response to acute injury is characterized by increased permeability of the blood-brain barrier (BBB) and pro-inflammatory microglia signaling, both of which have been linked to poor cognitive outcomes and neurological disease. The damaged BBB has increased leakiness, allowing serum proteins like fibrinogen into the brain, which interacts with local cells in a deleterious manner. At the same time, in response to injury, microglia demonstrate increased NLRP3 inflammasome activity and heightened release of pro-inflammatory cytokines. The relationship between increased fibrinogen uptake and microglial inflammasome signaling in the injured brain has not been well described. In this work, we investigate fibrinogen mediated NLRP3 inflammasome priming of BV-2 cells and primary adult microglia and propose a role for extracellular vesicles (EVs) as propagators of this interaction. Following exposure to fibrinogen microglia significantly upregulate transcription of IL-1β, IL-6, NLRP3 and other pro-inflammatory cytokines which was sustained by repeated fibrinogen exposure. Inhibition of fibrinogen mediated NLRP3 signaling was achieved at the transcriptional and assembly level using cannabidiol (CBD) and the NLRP3 inhibitor MCC950, respectively. EVs released following NLRP3 priming carry IL-1β, IL-18 mRNA and fibrinogen, propagate inflammatory signaling and can be detected in the circulation following BBB disruption in a preclinical stroke model. In conclusion, the interplay between fibrinogen extravasation, microglial NLRP3 signaling, and EV release can perpetuate chronic pro-inflammatory signaling and represents a novel method of inflammatory propagation
Cytisine—from Ethomedical use to the Development as a Natural Alternative for Smoking Cessation
- Author
- Anderson D.J.
- Barlow R.B.
- Barlow R.B.
- Bendorf S.
- Benndorf S.
- Bergmeier S.C.
- Bohler S.
- Brioni J.D.
- Changeux J.P.
- Clarke P.B.
- Creese I.
- Daleva L.
- Decker M.W.
- Dorsey G.A.
- Ferger B.
- Furet Y.
- Gentry C.L.
- Hall M.
- Hatfield G.M.
- Henningfield J.E.
- Imming P.
- Izaddoost M.
- Jonnala R.R.
- Karlin A.
- Keeler R.F.
- Laviolette S.R.
- Leyland A.
- Linville D.G.
- Marion L.
- Mitchell R.G.
- Murakoshi I.
- Museo E.
- N. Danchev
- Pabreza L.A.
- Papke R.L.
- Parker M.J.
- Paterson D.
- Paun D.
- Picciotto M.R.
- Rao T.S.
- Rao T.S.
- Rauwerda
- Reavill C.
- Reavill C.
- Richards H.G.
- Sariev A.K.
- Scharfenberg G.
- Schulters R.E.
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- V. Tzankova
- Wang F.
- Wenger B.W.
- White
- Wiegand T.S.
- Wood H.C.
- Zatonski W.
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
Genetics and smoking behavior
- Author
- A. Shields
- A. Strasser
- A.E. Shields
- A.S. Hamilton
- A.W. Bergen
- B.C. Haberstick
- C. Lerman
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- Caryn Lerman
- Center for Disease ControlPrevention
- Centers for Disease ControlPrevention
- Centers for Disease ControlPrevention
- D. Comings
- D. Wang
- D.E. Comings
- D.F. Gu
- D.J. Vandenbergh
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- D.T. Redden
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- E.J. Nestler
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- Terrance A. Johnson
- V. Malaiyandi
- V. Malaiyandi
- W.H. Berrettini
- X.Y. Lou
- X.Y. Lou
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Neurochemistry of Drug Abuse
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- Parker S.L.
- Parrott A.C.
- Parsons L.
- Parsons L.H.
- Partilla J.S.
- Paterson N.E.
- Paterson N.E.
- Patkar A.A.G.R.
- Pearl S.
- Peng X.
- Pennartz C.M.
- Pennings E.J.
- Perez-Reyes M.
- Peris J.
- Perkins K.A.
- Perry D.
- Pettit H.O.
- Pettit H.O.
- Pfeiffer A.
- Pfueller S.L.
- Picciotto M.R.
- Picciotto M.R.
- Pich E.
- Pidoplichko V.I.
- Pidoplichko V.I.
- Pierce R.C.
- Pierce R.C.
- Pietila K.
- Pifl C.
- Pilla M.
- Pistis M.
- Pitts D.
- Pluzarev O.
- Poddar M.K.
- Pogun S.
- Poindexter E.
- Poland R.E.
- Poland R.E.
- Pollack M.
- Poole R.
- Popik P.
- Porcu P.
- Post R.M
- Preseton K.L.
- Pristupa Z.B.
- Przewlocka B.
- Pubill D.
- Pudiak C.
- Pulvirenti L.
- Pögün S.
- Quirion R.
- Racke K.
- Ranaldi R.
- Ranaldi R.
- Ranaldi R.
- Ranaldi R.
- Rapier C.
- Rasmussen K.C.J
- Rausch J.
- Rawson R.A.
- Rawson R.A.
- Raynor K.
- Reid M.S.
- Reiger D.A.
- Reith M.
- Reith M.
- Reith M.
- Reith M.E.A.
- Reith M.E.A.
- Reith M.E.A.
- Reneman L.
- Ricaurte G.A.
- Ricaurte G.A.
- Ricaurte G.A.
- Ricaurte G.A.
- Ricaurte G.A.
- Rice M.E.
- Richardson N.
- Riddle E.L.
- Riegel A.C.
- Ritz M.
- Ritz M.C.
- Ritz M.C.
- Ritz M.C.
- Robbins T.W.
- Robbins T.W.
- Roberts D.
- Roberts D.
- Roberts D.C
- Roberts D.C.
- Roberts D.C.
- Roberts D.C.
- Robertson G.S.
- Robinson D.L.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robinson T.E.
- Robledo P.
- Rocha B.A.
- Rocha B.A.
- Rocher C.
- Rocio M.
- Rocio M.
- Rockhold R.
- Rockhold R.W
- Romero L.
- Rommelspacher H.
- Rose J.E.
- Rosin A.
- Rostene W.
- Rothman R.
- Rothman R.
- Rothman R.
- Rothman R.B.
- Rothman R.B.
- Rothman R.B.
- Rothman R.B.
- Rothman R.B.
- Rudnick G.
- Rukstalis M.
- Rush R.
- Russell M.A
- Russell V.A.
- Ruttenber A.J.
- Saal D.
- Sabol S.Z.
- Sakurai-Yamashita Y.
- Salminen O.
- Salminen O.
- Samson H.H.
- Samuel D.
- Sanchez C.J.
- Sanchez-Ramos J.
- Satel S.
- Satel S.
- Satel S.L.
- Satel S.L.
- Savelieva K.V.
- Scanzello C.R.
- Schechter M.D.
- Scheffel U.
- Scheffel U.
- Scheffel U.
- Schenk S.
- Schenk S.
- Schenk S.
- Schenk S.
- Schenk S.
- Schenk S.
- Schenk S.
- Schievelbein H.
- Schifano F.
- Schiffer W.K.
- Schilstrom B.
- Schmidt C.J.
- Schmidt C.J.
- Schmidt C.J.
- Schmidt C.J.
- Schmidt C.J.
- Schmidt C.J.
- Schneider N.G.O.R.
- Schoemaker H.
- Schroeder B.E.
- Schuckit M.A.
- Schuldiner S.
- Schultz W
- Schwartz K.
- Seiden L.S.
- Seiden L.S.
- Seiden L.S.
- Sekine Y.
- Self D
- Self D.
- Self D.W.
- Self D.W.
- Self D.W.
- Sellings L.H.
- Series H.G.
- Series H.G.
- Sershen H.
- Sesack S.R.
- Setola V.
- Shank R.P.
- Shankaran M.
- Shankaran M.
- Sharkey J.
- Shaya E.K.
- Shaywitz A.J.
- Shiah I.S.Y.L
- Shier W.T.
- Shiffman S.J.J.
- Shimada S.
- Shimosato K.
- Shippenberg T.
- Shippenberg T.
- Shippenberg T.
- Shippenberg T.
- Shoaib M.
- Shoaib M.
- Shoaib M.
- Shoblock J.R.
- Shoptaw S.
- Silva A.J.
- Simantov R.
- Simonin F.
- Sizemore G.M.
- Slikker W. Jr.
- Slusher B.
- Smith J.E.
- Smith R.C.
- Smolka M.N.
- Snyder G.L.
- Snyder S.H.
- Snyder S.J.
- Sokoloff P.
- Sonsalla P.K.
- Sora I.
- Sora I.
- Sorg B.A.
- Spampinato U.
- Spanagel R.
- Spanagel R.
- Spangler R.
- Spangler R.
- Spanos L.J.
- Sparks J.A.
- Sparrow D.
- Spealman R
- Spealman R.
- Spielwoy C.
- Spitz M.R.
- Sprague J.E.
- Sprouse J.S.
- Spyraki C.
- Spyraki C.
- Srisurapanont M.
- Staley J.
- Staley J.
- Staley J.
- Staley J.
- Staley J.
- Staley J.
- Staley J.
- Staley J.K.
- Staley J.K.
- Staley J.K.
- Staley J.K.
- Staley J.K.
- Stathis M.
- Stathis M.
- Steele T.D.
- Stefanski R.
- Stefanski R.
- Stefanski R.
- Stegmayr B.
- Steinbusch H.W.
- Steinpreis R.E.
- Stephens B.G.
- Stephens B.G.
- Stone D.M.
- Streeter C.C.
- Striplin C.D.
- Stromberg M.F.
- Strombom U.H.
- Suaad-Chagny M.F.
- Suemaru J.
- Sullivan P.F.
- Sulzer D.
- Sulzer D.
- Sulzer D.
- Sutherland G.
- Svingos A.L.
- Sweatt J.D
- Sweatt J.D
- Sweetnam P.
- Switzer R.C. III
- Szumlinski K.K.
- Takahashi S.
- Takaki M.
- Takaki M.
- Tan A.Y.
- Tancer M.
- Tapper A.R.
- Tella S
- Tennant F.
- Terwilliger R.Z.
- Tessari M.
- This
- Thomas G.M.
- Tolliver B.K.
- Tong J.
- Total
- Trujillo K.
- Trulson M.E.
- Tsukada H.
- Tucker G.J.
- Turek J.W.
- Turgeon S.M.
- Tzschentke T.M
- Ujike H.
- Ujike H.
- Ujike H.
- Ujike H.
- Ujike H.
- Ukai M.
- Ungerstedt U.
- Unterwald E.
- Unterwald E.
- Unterwald E.M
- Unterwald E.M.
- Uramura K.
- Vailati S.
- Valjent E.
- Valjent E.
- Valjent E.
- Van de Kar L.D.
- Vandenbergh D.J.
- Vaughan R.A.
- Vignon J.
- Villegier A.S.
- Villemagne V.
- Villemagne V.
- Vinklerova J.
- Volkow N.
- Volkow N.
- Volkow N.
- Volkow N.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Volkow N.D.
- Vollenweider F.X.
- Vollm B.A.
- Volz T.J.
- Wachtel H
- Wagner G.C.
- Wagner G.C.
- Walaas S.I.
- Wallace D.
- Walsh S.
- Walsh S.L.
- Walters C.L.
- Walters C.L.
- Wang F.
- Wang G.J.
- Wang G.J.
- Wang X.
- Wang X.
- Weddington W.W.
- Weintraub J.M.
- Weiss F.
- Wesson D.R
- West G.B.
- Westfall T.C.
- Wetli C.V.
- Wetli C.V.
- White C.R.
- White F.
- Whiteaker P.
- Wilson J.
- Wilson J.
- Wilson J.M.
- Wilson J.M.
- Wilson L.D.
- Wilson M.
- Winhusen T.M.
- Wise R.A
- Witkin J
- Witkin J.M.
- Witkin J.M.
- Wolf M.
- Wolf M.E.
- Wollemann M.
- Wong A.H.C.
- Wong G.
- Wonnacott S
- Wonnacott S.
- Wood M.D.
- Woodward J.J.
- Wooltorton J.R.
- Woolverton W.
- Woolverton W.L.
- Woolverton W.L.
- Worsley J.N.
- Worsley J.N.
- Wrona M.Z.
- Wu D.
- Wu J.
- Wu X.
- Xi Z.X.
- Xi Z.X.
- Xu Z.
- Yacoubian G.S. Jr.
- Yamamoto B.K.
- Yamamoto B.K.
- Yamashita H.
- Yan Q.S.
- Yan Z.
- Yeghiayan S.K.
- Yim H.J.
- Yokel R.A.
- Yoshimoto K.
- Yui K.
- Yui K.
- Yui K.
- Zachariou V.
- Zaczek R.
- Zaczek R.
- Zaczek R.
- Zeidonis D.
- Zeigler S.
- Zetterstrom T.
- Zhang D.
- Zhang H.
- Zhang X.
- Zhang X.Y.
- Zigmond M.J.
- Zimanyi I.
- Zito K.A.
- Zito K.A.
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study