GW2580 treatment after SCI in nonhuman primates preserves white matter ADC and modifies outcomes on myelinated fibers.
Ex vivo diffusion-weighted MRI rostral (A), within (B), and caudal (C) to the lesion 3 months after SCI in an untreated lemur. Schematic view of a T12-L1 lateral spinal cord hemisection (D). Schematic drawing of quantified parameters (E). Quantification 3 months following injury of the lesion percentage at the epicenter, the lesion extension and volume (area under the curve) (F). Ex vivo DW-MRI (G), longitudinal (H), and transverse (M) ADC mapping in treated and untreated animals. Red arrows in (G&H) indicate hyper-intense signal on both sides of the dorsal funiculus (DF) (untreated) and only on the hemisected side (GW2580). Longitudinal (I-J) diffusivities in the white matter and the DF. Quantifications were done rostral (I) and caudal (J) to the lesion epicenter. Quantification of LADC in the white matter (without DF) (K) and the DF (L) along the rostro-caudal axis. Schemes of the spinal cord at the lesion epicenter (N) and 2.1mm caudal to the lesion (O). CARS images (P-W') taken in insets area presented in N&O. Myelin organization after SCI in untreated (P-S') and GW2580-treated (T-W') primates at the lesion epicenter (P&P'; Q&Q'; T&T' and U-U') and caudal (R&R'; S&S'; V&V' and W&W') to the lesion. Images ipsilateral (P&P', T&T', R&R'; and V&V') and contralateral (Q&Q'; U&U', S&S'; and W&W') to the lesion. Insets in P-S and T-W correspond to higher magnifications in P'-S' and T'-W' respectively. Results for untreated nonhuman primates are in blue and GW2580-treated in green. Data are mean ± SEM per group. Student's unpaired t-test, *p < 0.05. Scale bars (A-C&G): 600µm; (P-S and T-W): 50 µm and (P'-S' and T'-W'): 20µm. Number of animals for MRI experiments: 5 untreated and 5 GW2580-treated and 1 animal in each group for CARS experiments.