Limb remote ischemic preconditioning protects the spinal cord from ischemia-reperfusion injury: a newly identified nonneuronal but reactive oxygen species-dependent pathway.
BACKGROUND
It remains to be established whether spinal cord ischemic tolerance can be induced by limb remote ischemic preconditioning (RIPC), and the mechanisms underlying the neuroprotective effects of RIPC on the spinal cord need to be clarified.


METHODS
Spinal cord ischemia was studied in New Zealand White rabbits. In experiment 1, all rabbits were subjected to 20-min spinal cord ischemia by aortic occlusion. Thirty minutes before ischemia, rabbits were subjected to sham intervention or RIPC achieved by bilateral femoral artery occlusion (10 min ischemia/10 min reperfusion, two cycles). Dimethylthiourea (500 mg/kg, intravenously), a hydroxyl radical scavenger, or vehicle was given 1 h before RIPC. Antioxidant enzyme activity was measured along with spinal cord histology and neurologic function. In experiment 2, rabbits were subjected to spinal cord ischemia, with or without RIPC. In addition, rabbits were pretreated with various doses of hexamethonium.


RESULTS
RIPC improved neurologic function and reduced histologic damage. This was associated with increased endogenous antioxidant activity. Dimethylthiourea inhibited the protective effects of RIPC. In contrast, there was no effect of hexamethonium on the protective effect of RIPC.


CONCLUSIONS
An initial oxidative stress acts as a trigger to upregulate antioxidant enzyme activity, rather than the neural pathway, and plays an important role in the formation of the tolerance against spinal cord ischemia by limb RIPC.
Dong
Hai-Long
HL
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Zhang
Yi
Y
Su
Bin-Xiao
BX
Zhu
Zheng-Hua
ZH
Gu
Qiu-Han
QH
Sang
Han-Fei
HF
Xiong
Lize
L
D000818:Animals; D002374:Catalase / Q000378:metabolism; D005121:Extremities / Q000098:blood supply*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009068:Movement / Q000502:physiology; D009460:Neurologic Examination; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea