Synergistic Pharmacological Therapy to Modulate Glial Cells in Spinal Cord Injury.

Current treatments for modulating the glial-mediated inflammatory response after spinal cord injury (SCI) have limited ability to improve recovery. This is quite likely due to the lack of a selective therapeutic approach acting on microgliosis and astrocytosis, the glia components most involved after trauma, while maximizing efficacy and minimizing side effects. We have developed and characterized a new nanogel that can selectively release active compounds in microglial cells and astrocytes. We evaluated the degree of selectivity and subcellular distribution of the nanogel by applying an innovative super-resolution microscopy technique, expansion microscopy. We then tested two different administration schemes in a SCI mouse model: in an early phase, the nanogel loaded with Rolipram, an anti-inflammatory drug, achieved significant improvement in the animal's motor performance due to the increased recruitment of microglia and macrophages that were able to localize the lesion. Treatment in the late phase, however, gave opposite results, with worse motor recovery because of the widespread degeneration. These findings demonstrate that the nanovector can be selective and functional in the treatment of the glial component in different phases of SCI. They also open a new therapeutic scenario for tackling glia-mediated inflammation after neurodegenerative events in the central nervous system. This article is protected by copyright. All rights reserved.