We investigated vascular changes after stroke using magnetic resonance imaging (MRI) microvascular density (MVD) measurement. T 2 and were measured in eight rats before and after injecting an intravascular superparamagnetic iron oxide contrast agent to derive the corresponding transverse relaxation shift. Reliability of MRI for measurement of MVD was compared with corresponding sections immunostained with von Willebrand factor (vWF) 2 weeks after stroke. The intracorrelation coefficient (ICC) and its 95% lower bound (LB) was high in the ischemic recovery region (ICC = 0.753), moderate in the contralateral area of normal brain tissue (ICC = 0.70), and low in the ischemic core (ICC = 0.24). A very good agreement (ICC = 0.85) and correlation (r = 0.90) were observed using only the recovery region and normal contralateral hemisphere (ICC = 0.85; 95% LB = 0.78; P < 0.05). The mean MRI MVD in the center of the core lesion (26±9 per mm 2 ) was lower than in the recovery region (209±60 per mm 2 ) or contralateral normal hemisphere (313±32 per mm 2 ). However, large errors in MRI MVD were encountered in the ischemic core. Our data demonstrate that MRI MVD measurements can quantitatively evaluate microvascular changes in the brain tissue after stroke, if the MVD is not extremely low as in the ischemic core.

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Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice. Male C57BL/6 mice fed 0.3% cuprizone for 12 weeks exhibited CC atrophy with chronic demyelination, astrogliosis, and microglial activation. Syngeneic iNSCs were transplanted into the CC after ending cuprizone and perfused for neuropathology 2 weeks later. Magnetic resonance imaging (MRI) sequences for magnetization transfer ratio (MTR), diffusion-weighted imaging (T2), and diffusion tensor imaging (DTI) quantified CC pathology in live mice before and after iNSC transplantation. Each MRI technique detected progressive CC pathology. Mice that received iNSCs had normalized DTI radial diffusivity, and reduced astrogliosis post-imaging. A motor skill task that engages the CC is Miss-step wheel running, which demonstrated functional deficits from cuprizone demyelination. Transplantation of iNSCs resulted in marked recovery of running velocity. Neuropathology after wheel running showed that iNSC grafts significantly increased host oligodendrocytes and proliferating oligodendrocyte progenitors, while modulating axon damage. Transplanted iNSCs differentiated along astrocyte and oligodendrocyte lineages, without myelinating, and many remained neural stem cells. Our findings demonstrate the applicability of neuroimaging and functional assessments for pre-clinical interventional trials during chronic demyelination and detect improved function from iNSC transplantation. Directly reprogramming fibroblasts into iNSCs facilitates the future translation towards exogenous autologous cell therapies.