TY - JOUR
T1 - Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice
AU - López-Vales, Rubèn
AU - Redensek, Adriana
AU - Skinner, Thomas A.A.
AU - Rathore, Khizr I.
AU - Ghasemlou, Nader
AU - Wojewodka, Gabriella
AU - De Sanctis, Juan B.
AU - Radzioch, Danuta
AU - David, Samuel
PY - 2010/3/3
Y1 - 2010/3/3
N2 - The inflammatory response is thought to contribute to secondary damage after spinal cord injury (SCI). Polyunsaturated fatty acids (PUFAs) play an important role in the onset and resolution of inflammation. Arachidonic acid (AA), an ω-6 PUFA, contributes to the initiation of inflammatory responses, whereas docosahexaenoic acid (DHA), an ω-3 PUFA, has antiinflammatory effects. Therefore, decreasing AA and increasing DHA levels after SCI might be expected to attenuate inflammation after SCI and promote tissue protection and functional recovery. We show here that daily oral administration of fenretinide after spinal cord contusion injury led to a significant decrease in AA and an increase in DHA levels in plasma and injured spinal cord tissue. This was accompanied by a significant reduction in tissue damage and improvement in locomotor recovery. Fenretinide also reduced the expression of proinflammatory genes and the levels of oxidative stress markers after SCI. In addition, in vitro studies demonstrated that fenretinide reduced TNF-α (tumor necrosis factor-α) expression by reactive microglia. These results demonstrate that fenretinide treatment after SCI can reduce inflammation and tissue damage in the spinal cord and improve locomotor recovery. These beneficial effects may be mediated via the ability of fenretinide to modulate PUFA homeostasis. Since fenretinide is currently in clinical trials for the treatment of cancers, this drug might be a good candidate for the treatment of acute SCI in humans. Copyright © 2010 the authors.
AB - The inflammatory response is thought to contribute to secondary damage after spinal cord injury (SCI). Polyunsaturated fatty acids (PUFAs) play an important role in the onset and resolution of inflammation. Arachidonic acid (AA), an ω-6 PUFA, contributes to the initiation of inflammatory responses, whereas docosahexaenoic acid (DHA), an ω-3 PUFA, has antiinflammatory effects. Therefore, decreasing AA and increasing DHA levels after SCI might be expected to attenuate inflammation after SCI and promote tissue protection and functional recovery. We show here that daily oral administration of fenretinide after spinal cord contusion injury led to a significant decrease in AA and an increase in DHA levels in plasma and injured spinal cord tissue. This was accompanied by a significant reduction in tissue damage and improvement in locomotor recovery. Fenretinide also reduced the expression of proinflammatory genes and the levels of oxidative stress markers after SCI. In addition, in vitro studies demonstrated that fenretinide reduced TNF-α (tumor necrosis factor-α) expression by reactive microglia. These results demonstrate that fenretinide treatment after SCI can reduce inflammation and tissue damage in the spinal cord and improve locomotor recovery. These beneficial effects may be mediated via the ability of fenretinide to modulate PUFA homeostasis. Since fenretinide is currently in clinical trials for the treatment of cancers, this drug might be a good candidate for the treatment of acute SCI in humans. Copyright © 2010 the authors.
U2 - https://doi.org/10.1523/JNEUROSCI.5770-09.2010
DO - https://doi.org/10.1523/JNEUROSCI.5770-09.2010
M3 - Article
VL - 30
SP - 3220
EP - 3226
ER -
