Early Nrf2/HO-1 signaling activation following surgical decompression in a rat model of lumbar spinal stenosis-induced neurogenic intermittent claudication

Abstract Lumbar spinal stenosis is a prevalent degenerative disease globally. The hallmark symptom is neurogenic intermittent claudication, characterized by lower extremity pain during walking that is relieved by resting.Although mechanical constriction initiates the primary pathology, the precise molecular orchestration underlying this transient, rest-induced symptomatic resolution has not yet been fully characterized. We established a cauda equina compression model in Sprague-Dawley rats using epidural silicone implants. Multiple groups were designed to evaluate behavioral, histological, and molecular changes across the acute and chronic compression phases, as well as designated post-decompression recovery windows. Chronic compression induced functional impairment, structural injury, oxidative stress, and neuroinflammation. At 2 h after surgical decompression, Nrf2 showed increased nuclear localization together with early upregulation of Ho-1, Nqo1, and Gclc. Under continued compression, SFN improved selected functional and molecular injury indices, whereas ML385 treatment was associated with worsened neurological, inflammatory, and apoptotic outcomes. Nrf2/HO-1 signaling may contribute to the early antioxidant response following surgical decompression and may represent a potential pharmacological target for compression-associated cauda equina injury.