Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.

Abstract

The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.

• Authors: Xiaoliang Wang, Juan Pablo de Rivero Vaccari, Handong Wang, Paulo Diaz, Ramon German, Alex E Marcillo, Robert W Keane
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 29 Issue 5 Pg. 936-45 (Mar 20 2012) ISSN: 1557-9042 [Electronic] United States
• PMID: 21806470 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Isothiocyanates
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Sulfoxides
• Thiocyanates
• sulforaphane

Topics

• Animals
• Disease Models, Animal
• Female
• Immunoblotting
• Immunohistochemistry
• Isothiocyanates
• Motor Activity (drug effects, physiology)
• NF-E2-Related Factor 2 (metabolism)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Inbred F344
• Response Elements (physiology)
• Signal Transduction (drug effects, physiology)
• Spinal Cord Injuries (metabolism, physiopathology)
• Sulfoxides
• Thiocyanates (pharmacology)