TY - JOUR
T1 - Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury
AU - Vismara, Irma
AU - Papa, Simonetta
AU - Veneruso, Valeria
AU - Mauri, Emanuele
AU - Mariani, Alessandro
AU - De Paola, Massimiliano
AU - Affatato, Roberta
AU - Rossetti, Arianna
AU - Sponchioni, Mattia
AU - Moscatelli, Davide
AU - Sacchetti, Alessandro
AU - Rossi, Filippo
AU - Forloni, Gianluigi
AU - Veglianese, Pietro
PY - 2020/1/28
Y1 - 2020/1/28
N2 - 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.
AB - 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.
U2 - 10.1021/acsnano.9b05579
DO - 10.1021/acsnano.9b05579
M3 - Article
C2 - 31887011
VL - 14
SP - 360
EP - 371
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 1
ER -