Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury

Irma Vismara, Simonetta Papa, Valeria Veneruso, Emanuele Mauri, Alessandro Mariani, Massimiliano De Paola, Roberta Affatato, Arianna Rossetti, Mattia Sponchioni, Davide Moscatelli, Alessandro Sacchetti, Filippo Rossi, Gianluigi Forloni, Pietro Veglianese

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Abstract

Astrogliosis has a very dynamic response during the progression of spinal cord injury, with beneficial or detrimental effects on recovery. It is therefore important to develop strategies to target activated astrocytes and their harmful molecular mechanisms so as to promote a protective environment to counteract the progression of the secondary injury. The challenge is to formulate an effective therapy with maximum protective effects, but reduced side effects. In this study, a functionalized nanogel-based nanovector was selectively internalized in activated mouse or human astrocytes. Rolipram, an anti-inflammatory drug, when administered by these nanovectors limited the inflammatory response in A1 astrocytes, reducing iNOS and Lcn2, which in turn reverses the toxic effect of proinflammatory astrocytes on motor neurons in vitro, showing advantages over conventionally administered anti-inflammatory therapy. When tested acutely in a spinal cord injury mouse model, it improved motor performance, but only in the early stage after injury, reducing the astrocytosis and preserving neuronal cells.

Original languageEnglish
Pages (from-to)360-371
Number of pages12
JournalACS Nano
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 28 2020

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Vismara, I., Papa, S., Veneruso, V., Mauri, E., Mariani, A., De Paola, M., Affatato, R., Rossetti, A., Sponchioni, M., Moscatelli, D., Sacchetti, A., Rossi, F., Forloni, G., & Veglianese, P. (2020). Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury. ACS Nano, 14(1), 360-371. https://doi.org/10.1021/acsnano.9b05579