Table 1.

Fibrin(ogen) cellular targets at the NVU in neurologic diseases.

Target	Functions	Receptors/Signaling pathways	Model	Reference
Resident cells
Microglia	Activation	CD11b/CD18	In vitro: microglia cultures	Adams et al. (2007)
	– Phagocytosis	RhoA, Akt, PI3K		Davalos et al. (2012)
	– Perivascular clustering		In vivo: EAE; FIE, AD animal models	Ryu et al. (2015)
	– Chemokine and proinflammatory gene expression			Paul et al. (2007)
	– ROS release
Astrocytes	Gliosis	TGFβ, Smad2, CSPGs	In vivo: stab wound injury; cortical fibrinogen injection	Schachtrup et al. (2010)
	– Scar formation	CSPGs
Neurons	– Axonal damage	β3-integrin, EGFR	In vitro: neuronal cultures	Schachtrup et al. (2007)
	– Inhibition of neurite outgrowth			Davalos et al. (2012)
			In vivo: EAE, spinal cord injury, ischemic stroke	Ill-Raga et al. (2015)
Endothelial cells	– Increased permeability	ICAM-1, α5β1 F-actin, TJ proteins, MEK, ERK, VE-cadherin, fibrin fragment E and Bβ15–42, RhoGTPase	In vitro: endothelial cell cultures	Tyagi et al. (2008)
	– Infiltration of leukocytes			Patibandla et al. (2009)
				Jennewein et al. (2011)
				Muradashvili et al. (2011)
CNS infiltrating cells
T cells	– Recruitment	APC CD11b/CD18	In vitro: T cell/APC co-cultures	Ryu et al. (2015)
	– Activation	CXCL10, IL12, IFN-γ
	– Proliferation		In vivo: FIE; 2D2 TCR MOG transgenic mice
	– Th1 differentiation
Macrophages	– Recruitment	CD11b/CD18	In vitro: macrophage cultures	Ryu et al. (2015)
	– Chemokine expression	TLR4		Smiley et al. (2001)
	– Infiltration	CXCL10, CCL2, MCP-1	In vivo: FIE