[O-2-244] SPIO-Induced Signal Changes Correlated with EAE Development in the Lower Lumbar Spinal Cord
[Objective] Recent study showed auto reactive T cells accumulate in the fifth lumbar spinal cord in experimental autoimmune encephalomyelitis (EAE) mice, animal model of human multiple sclerosis1). The contribution of other immune cells such as macrophages in EAE is not clear. We reported that high-field MRI with superparamagnetic particles of iron oxide (SPIO) can be use to monitor the recruitment of peripheral macrophages into the mouse brain2). Here we assessed whether macrophages are recruited or not into the spinal cord in EAE mice by using MRI with SPIO injection.
[Methods] EAE and control mice were used in this study. EAE was induced by myelin oligodendrocyte glycol peptide and complete Freund's adjuvant mixed emulsion injection. SPIO (Resovist, I’rom pharma) was injected from tail vein (100 uL/mouse) at each timing correlated the EAE clinical stage. MRI scans were done one day after SPIO injection by 11.7 T Biospec (Bruker) with T2*W-FLASH sequence. After in vivo study, we carried out high-resolution ex vivo scans after perfusion fixation. The existence of SPIO and macrophages was confirmed histologically.
[Results & Discussion] We found specific signal changes in the spinal cord of EAE mice, correlated with the development of EAE. We also found the higher number of SPIO-induced black spots in the spinal cord of EAE group as compared with control. These spots were also detected on ex vivo exam and corresponded to the distribution of macrophage. These results suggest that EAE-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that high-field MRI with SPIO enables the detection of pathological alterations in EAE.
[References] 1) Arima et al., Cell, 148:447-457 (2012), 2) Mori et al., 41st JSMRM, P-2-086 (2013).
[Methods] EAE and control mice were used in this study. EAE was induced by myelin oligodendrocyte glycol peptide and complete Freund's adjuvant mixed emulsion injection. SPIO (Resovist, I’rom pharma) was injected from tail vein (100 uL/mouse) at each timing correlated the EAE clinical stage. MRI scans were done one day after SPIO injection by 11.7 T Biospec (Bruker) with T2*W-FLASH sequence. After in vivo study, we carried out high-resolution ex vivo scans after perfusion fixation. The existence of SPIO and macrophages was confirmed histologically.
[Results & Discussion] We found specific signal changes in the spinal cord of EAE mice, correlated with the development of EAE. We also found the higher number of SPIO-induced black spots in the spinal cord of EAE group as compared with control. These spots were also detected on ex vivo exam and corresponded to the distribution of macrophage. These results suggest that EAE-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that high-field MRI with SPIO enables the detection of pathological alterations in EAE.
[References] 1) Arima et al., Cell, 148:447-457 (2012), 2) Mori et al., 41st JSMRM, P-2-086 (2013).