FIG. 6.
Early systemic administration of PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) attenuates neurodegeneration and apoptosis inducing factor (AIF) release after trsumatic brain injury (TBI). (A) Immunocytochemistry showed that vehicle-treated animals had decreased expression of MAP2 (a marker of neuronal viability; red channel) 72 h after trauma. TO-PRO-3 counterstaining (blue channel) demonstrates that cells are present in the contusion area. In comparison, animals that received systemic administration of PJ34 starting at 3 h post-TBI demonstrated increased MAP2 signal. (B) Immunocytochemistry also showed that vehicle-treated animals had increased in the AIF signal intensity 72 h after trauma reflecting the release of the pro-apoptotic protein AIF from mitochondria, a key step in the activation of AIF-mediated cell death. In comparison, animals that received systemic administration of PJ34 starting at 3 h post-TBI demonstrated decreased AIF staining intensity. Higher magnification images indicate the transition of cortical AIF immunofluorescence from punctate cytosolic in sham animals to diffuse (including the nuclear area) distribution in injured animals. PJ34 treatment attenuated these changes. CCI, controlled cortical impact. Color image is available online at www.liebertpub.com/neu