Figure 4. Fibrinogen induces microglial responses in the healthy mouse cortex in vivo.

(a) Local injection of fibrinogen (3–6 mg ml⁻¹, red) in the cortex of the Cx3cr1^GFP/+ mice causes microglial process extension (green) toward the tip of the injection electrode; control electrodes containing ACSF, or albumin (5 mg ml⁻¹) caused little or no microglial responses. Quantification of microglial responses over 30 min toward the tip of the electrode upon injection of ACSF (n=7), albumin (n=6), or fibrinogen (n=9). (*P<0.05, **P<0.01, ***P<0.001, two-way analysis of variance (ANOVA)). Scale bar, 10 μm. See corresponding Supplementary Movie 5. (b) Sustained and prolonged microglial response in mouse cortex after a single injection of fibrinogen. Fibrinogen injected at a high concentration (6–10 mg ml⁻¹, red) forms a deposit that is surrounded by microglial processes. The size of the fibrin deposit remains unaltered, and the microglial response to fibrin persists for at least 6 h. Scale bar, 10 μm. (c) Microglial immunoreactivity (Iba-1, red) and quantification from mouse brain sections 3 days after stereotactic injections of fibrinogen, ACSF or albumin protein control, or plasma isolated from wt, Fib^−/−, Fib^γ390-396A mice (n=6 mice per condition). Bar graph represents mean±s.e.m. (*P<0.05, **P<0.01, one-way ANOVA). Scale bar, 300 μm.