Figure 6.

Fluorescent imaging of cerebral cortex (coronal view) in rats with compromised blood-brain barrier 1 week after i.v. injection of Frema594. (a) Cerebral cortex near the penetration of the recording electrode. Note that a positive red signal is barely detected (arrowheads). (b) Fluorescent images of the cortex at least 2 mm away from the recording electrode or CSD-induction electrode. (c) Fluorescent images of the cortex near the CSD-induction electrode. Note distinct Frema594 labeling in the pia (arrowheads), along the track of the CSD-induction electrode but not along the track of the recording electrode in (a). (d) High magnification images of the areas framed in (c) (right column), showing red and green channels and a superimposition of both images. Note that the pia is visible in red but not green channel images, confirming Frema594 presence in the pia of rats with compromised BBB. Also note that in the cortex, there are axons (arrowheads) that are labeled in red but not green channel images, raising the possibility that fremanezumab may be able to enter broken axons near a brain lesion. Signal in the green channel (middle) represents auto-fluorescence that is typical to formation of post-lesion gliosis. Small images in red were acquired at default exposure. Small images in green and large images in red (right and left columns) are overexposed for reference and visualization of anatomical structures. Dotted rectangles in small images depict enlarged images shown in red.