Spinal cord ischemia-reperfusion injury (SCIRI) is a serious complication in veterinary practice, particularly following aortic cross-clamping during equine colic surgery, with no proven therapies for its neurological sequelae. Autophagy and ferroptosis drive SCIRI pathogenesis, but DOCK2’s role remains unclear. We investigated DOCK2 using 110 male C57BL/6 wild-type (WT, n=6/group) and 6 DOCK2-deficient (DOCK2-KO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated primary spinal neurons. Murine SCIRI was induced by clamping the abdominal aorta and spinal cord DOCK2 expression was increased post SCIRI, peaking at 24 h. DOCK2 deficiency also enhanced viability by 40% of primary spinal neurons under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. SCIRI mice exhibited improved motor function recovery, reduced spinal cord pathological damage following DOCK2 knockdown. Mechanistically, we revealed that DOCK2 deficiency suppressed excessive ferroptosis-mediated by autophagy in vivo and in vitro. Notably, the protective effects of DOCK2 deficiency were abolished by autophagy activator rapamycin. Moreover, sevoflurane pretreatment exerted a protective effect against SCIRI, which was abrogated by DOCK2 overexpression. In conclusion, DOCK2 mediates SCIRI via autophagy-dependent ferroptosis and is a potential therapeutic target. Sevoflurane protects against SCIRI by inhibiting DOCK2, providing a basis for perioperative SCIRI management in animals.

To Cite This Article: Huijun Liu, Yu Li, Junya Li, Tengfei Wu, Jinpeng Liu, Hongnan Wang and Jie Han, 2025. DOCK2 deficiency alleviates murine spinal cord ischemia-reperfusion injury via inhibiting autophagy-dependent ferroptosis and the modulatory role of sevoflurane pretreatment. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.295