Analysis of cortical plasticity after spinal cord injury using resting state-fMRI

We have reported the effectiveness of cell transplantation therapy for spinal cord injury (SCI) using neural stem cells (NS cells) and induced pluripotent stem cells (iPS cells). However, the mechanisms of functional recovery as well as reconstruction of neuronal network remain to be elucidated. Recent studies have demonstrated that SCI changed the state of large cortical networks. SCI leads to atrophy of primary motor and sensory cortex, and then reorganization of the sensorimotor system occurs(Freund P. Brain 2011), which was detected by the functional magnetic resonance imaging (fMRI). However, few studies have reported SCI related functional changes of the cortex in detail. Here we analyze the relations between the cortical plasticity and the functional improvement after SCI using resting state- fMRI.

Four C57BL6 female mice were subjected to resting-state fMRI. After careful acclimation to environmental stress, MRI was performed using a 7.0-Tesla MRI apparatus equipped with actively shielded gradients at maximum strength of 700mT/m (Biospec ; 70/16 Brucker Biospin ) with CryoProbe (Brucker BioSpin AG). Mice received complete spinal cord transections at the Th9/10 level using a surgical blade. The severed ends of the cord were inspected under a surgical microscope carefully to ensure complete transection. MRI was performed before and two weeks after SCI. MRI data analysis was performed using SPM12 software and CONN toolbox. This consisted of head movement correction, adjustments of acquisition timing across slices, and smoothing. Structural and functional images were spatially normalized to a standard structural brain averaged from C57BL6 mice (n=20). Functional connectivity was analyzed based on the AMBMC labels (Ulmann, JFP,et al. Neuroimage 2013).

First we successfully detected the normal functional brain network connectivity (FBNC) using fMRI in the mice before SCI. Then we compared the change of FBNC before and after SCI. The bilateral primary somatosensory area changed the synchronicity after SCI. In addition, the bilateral primary motor cortex has connected with contralateral cingulate area strongly in the normal mice, but the primary motor cortex has connected strongly with another area in the mice after SCI.

These results demonstrate that it is feasible to analyze FBNC of mice using fMRI. Our findings also provide the evidence that SCI induced FBNC alterations in the brain cortex. In the future, we would like to take fMRI in various degree of SCI model to explore the specific spatial and temporal pattern of brain functional changes after SCI.

Society for Neuroscience Chicago Nanosymposium Advances in SCI Research and Plasticity

Authors: *K. MATSUBAYASHI1, A. IWANAMI1, J. KOHYAMA2, Y. KOMAKI3, M. MATSUMOTO1, H. OKANO2, M. NAKAMURA1; 1Orthopaedic Surgery, 2Physiol., Keio Univ. Sch. of Med., Tokyo, Japan; 3Central Inst. for Exptl. Animals, Kawasaki, Japan

Disclosures: K. Matsubayashi: None. A. Iwanami: None. J. Kohyama: None. Y. Komaki: None. M. Matsumoto: None. H. Okano: None. M. Nakamura: None.

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