Transplanted Adult Neural Stem Cells Express Sonic Hedgehog In Vivo and Suppress White Matter Neuroinflammation after Experimental Traumatic Brain Injury

Figure 5

Induced genetic in vivo labeling of host cells expressing Gli1 in the subventricular zone (SVZ) following traumatic brain injury (TBI) and NSC transplantation. Timeline for Gli1^CreERT2;R26tdTomato host mice (a) with diagrams of TBI and injection site (b) and the SVZ region quantified (c) in naïve, sham, or TBI conditions. NSC-GFP cells for transplantation were isolated from mice constitutively expressing green fluorescent protein. (d–f) Quantification of cells actively responding to canonical Shh signaling (Gli1-Tom cells), in the SVZ showed no significant change in naïve (d), sham (e), or TBI (f) mice following injection of NSC-GFP as compared to vehicle. Low magnification images of the full SVZ regions are provided in Figure S. (g–l) NSC-GFP cells transplanted into the lateral ventricle (LV) nestled within the choroid plexus (g) or adhered to the walls of the lateral ventricles (h, i) and were also found within the third ventricle (j). Gli1-Tom-labeled cells are not evident in the corpus callosum (cc). In contrast, robust Gli1-Tom label cells are found in the SVZ and in the cortex. Higher magnification of cells shown at the arrows (h, i). One cell has processes extended around the ependymal cell layer ((k), inset). Scale bars = 1 mm (b), 400 μm (c), 200 μm (g–j), 50 μm (k, l). Quantification included cohorts of naïve + vehicle (), naïve + NSC-GFP (), sham + vehicle (), sham + NSC-GFP (), TBI + vehicle (), and TBI + NSC-GFP ().