Work

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

Year: 2026

Type: article

Abstract: Background: 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. Methods: 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. Results: Chronic compression induced local venous stasis, triggering oxidative stress and neuroinflammation. Upon decompression simulating a resting state, rapid nuclear translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) occurred. This event activated downstream heme oxygenase-1 (HO-1) expression, effectively clearing reactive oxygen species and mitigating inflammation. Pharmacological intervention using sulforaphane mimicked this protective effect without surgical decompression, whereas the inhibitor ML385 abolished the natural recovery process. Conclusion: The cyclic ischemia-reperfusion process inherent to intermittent claudication dynamically triggers the Nrf2/HO-1 endogenous antioxidant pathway during the rest phase. Targeting this pathway offers a potential molecular strategy for the non-surgical management of lumbar spinal stenosis. Clinical trial number: not applicable.

Source: Scientific Reports

DOI: 10.1038/s41598-026-71139-4