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

Figure 6

NSC transplantation into the lateral ventricle (LV) following traumatic brain injury (TBI) suppresses injury-induced neuroinflammation in the corpus callosum. (a) Experimental diagram showing corpus callosum (cc) and cingulum regions (cg) quantified at the coronal level of the anterior commissure (ac) for mice prepared as detailed in Figures 5 and S. Mice were analyzed at two weeks after NSC/vehicle injection which was four weeks after TBI/sham surgery. (b–d) Axons in the cingulum cut through transversely exhibit immunoreactivity for total neurofilaments (green) or SMI-32 (red) to detect nonphosphorylated neurofilaments as an indicator of axon damage. SMI-32-labeled axons are significantly increased in TBI, as compared to sham mice (d). (e–g) Coronal sections of the corpus callosum immunostained for GFAP to detect astrocytes (green, arrowheads) and Cd11b to identify microglia/macrophages (red, arrows) with DAPI nuclear stain (blue). As compared to sham mice (e), immunoreactivity for reactive changes in GFAP and CDllb is evident after TBI (f) and attenuated in TBI mice with NSC transplantation (g). (e’, f’, and g’) Quantification of neuroinflammation in the corpus callosum. Immunoreactivity for GFAP (e’) and CD11b (f’, g’) was significantly increased in mice with TBI. NSC-GFP transplantation following TBI significantly reduced GFAP (e’) and CD11b (f’) immunoreactivity. Scale bar = 1 mm (a), 20 μm (b), 100 μm (e). Quantification included cohorts of sham + vehicle (), sham + NSC-GFP (), TBI + vehicle (), TBI + NSC-GFP ( for neurofilaments; for CDllb GFAP).