Diffusion Tensor Imaging Evaluation of Axonal/White Matter Remodeling in a Mouse Model of Diabetic Stroke Treated with Novel p38 MAPK Inhibitor, VCP979.

Type 2 diabetes mellitus (T2DM) is associated with severe axonal/white matter (WM) injury and poor functional outcomes following ischemic stroke. T2DM induces activation of p38 mitogen-activated protein kinases (MAPKs), which may be linked to the axonal/WM damage. In the present study, adult male C57BL/6J mice with streptozotocin (STZ)-induced T2DM mice were subjected to photothrombotic ischemic stroke and treatment with p38 MAPK inhibitors. The novel p38 MAPK inhibitor, VCP979, significantly promoted axonal/WM remodeling, neural progenitor cell migration, and improved functional recovery in T2DM mice. In vivo diffusion tensor imaging (DTI) revealed that the fractional anisotropy (FA) value, fiber number ratio, and fiber length were increased in the VCP979-treated group. Thus, VCP979 improves axonal/WM remodeling and functional outcomes in a diabetic mouse stroke model. DTI may aid in visualizing axonal/WM remodeling and evaluating the therapeutic efficacy of VCP979.