Preventive and therapeutic effects of Tanshinone IIA on spinal cord injury without radiographic abnormality by regulating microglial phenotype polarization.

Spinal cord injury without radiographic abnormality (SCIWORA) occurs in patients with cervical spinal stenosis (CSS) following minor trauma, often leading to significant neurological deficits. While surgical decompression reduces SCIWORA risk, some patients are ineligible or reluctant to undergo surgery. Consequently, reducing the risk of SCIWORA in the absence of surgical intervention and optimizing spinal cord function recovery remain pivotal challenges. This study explores the potential of Tanshinone IIA (TIIA) in preventing and treating SCIWORA by modulating microglial polarization and attenuating neuroinflammation. Asymptomatic CSS was induced in Sprague-Dawley rats by implanting hydrogels into the spinal canal for four weeks, followed by mild cervical trauma using the NYU Impactor. Rats were divided into sham, SCIWORA, prevention, and prevention + treatment groups. Preventive administration of TIIA significantly alleviated motor and histological damage, notably reducing glial scar formation and neuronal, myelin, and microvascular degeneration associated with SCIWORA. TIIA also inhibited the activation of pro-inflammatory M1 microglia while promoting the expansion of anti-inflammatory M2 microglia. Continued TIIA treatment after SCIWORA further enhanced motor function recovery, improved spinal cord tissue repair, provided ongoing protection to neurons, myelin, and microvasculature, reduced glial scar formation, modulated microglial polarization, inhibited NF-κB signaling pathway activation, and reduced neuroinflammation. These findings suggest that TIIA may serve as a non-surgical strategy to mitigate SCIWORA risk and promote recovery after SCIWORA in rats.