Sulforaphane enhances locomotor recovery after spinal cord injury through antioxidant, anti-inflammatory, and JAK/STAT-modulating mechanisms.

Spinal cord injury (SCI) leads to irreversible neurological deficits primarily through secondary injury mechanisms, including oxidative stress and glial dysfunction. Sulforaphane (SFN), a naturally occurring isothiocyanate, has shown antioxidant and anti-inflammatory effects in various neurological models, but its impact on Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and microglial polarization in SCI remains unclear. Adult male Wistar rats were randomly assigned to Sham, SCI, or SCI + SFN groups (n = 10/group). SCI was induced by a moderate T10 contusion, and SFN (50 mg/kg, i.p.) was administered at 10 min, 72 h, and 7 days post-injury. Locomotor recovery was assessed using the Basso-Beattie-Bresnahan (BBB) scale. At day 14, spinal cord tissue was analyzed for oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), as well as JAK2/STAT3 signaling and microglial polarization. SCI significantly increased ROS and MDA levels while reducing SOD activity and GSH content. Phosphorylation of JAK2 and STAT3, along with glial fibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), was markedly elevated. SFN treatment restored antioxidant defenses, suppressed JAK2/STAT3 activation, partially recovered suppressor of cytokine signaling 3 (SOCS3), and reduced pro-inflammatory responses. Moreover, SFN shifted microglial polarization from a pro-inflammatory (M1) toward a reparative (M2) phenotype and significantly improved BBB locomotor scores compared with untreated SCI rats. SFN confers neuroprotection in SCI by reducing oxidative stress, modulating JAK/STAT signaling, rebalancing microglial polarization, and improving locomotor recovery. These findings highlight SFN as a promising candidate for therapeutic development in SCI.