Inna Bukreeva, Michela Fratini, Gaetano Campi, Raffaele Spanò, Valentina Petrosino, Ranieri Cancedda, Nicole Kerlero de Rosbo, Antonio Uccelli, Alberto Bravin, Maddalena Mastrogiacomo and Alessia Cedola
Institute of Nanotechnology, Laboratory of Soft and Living Matter-CNR, c/o Physics Department at ‘Sapienza’ University, Piazzale Aldo Moro 2, 00185 Rome, Italy
We apply X-ray Synchrotron Phase Contrast Tomography (XSPCT) to the 3D imaging of Vascular Network (VN) and Neuronal System (NS) in mouse spinal cord for the investigation of neurodegenerative diseases. We demonstrate the capability of XSPCT to simultaneously visualize the three-dimensional VN and NS of mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, without contrast agent and without a destructive sample preparation, which could lead to data misinterpretation.
The present work mainly focuses on the pre-clinical study, by XSPCT, of spinal cord from mice with experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. We investigate 3D distribution of the axons fibers, glia and neuron cells of NS, together with the vascular tree and micro-capillaries network. We compare healthy samples, untreated EAE affected samples and EAE affected samples treated by i.v. injection with mesenchymal stem cells, a subset of adult progenitor cells with immunomodulatory and neuroprotective properties, which ameliorate EAE and are being considered as alternative therapy for neurological diseases.
The comparison between tissues from control mice, mice affected with EAE and treated mice shows the relationship between blood-spinal cord-barrier impairment and neuroinflammation, and shows how this relationship is affected by treatment with mesenchymal stem cells.