Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.
BACKGROUND
Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process.


METHODS
EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay.


RESULTS
The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion.


CONCLUSIONS
These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.
Wang
Qiang
Q
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Ding
Qian
Q
Zhou
Yiming
Y
Gou
Xingchun
X
Hou
Lichao
L
Chen
Shaoyang
S
Zhu
Zhenghua
Z
Xiong
Lize
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D004396:Coloring Agents; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000502:physiology; D006609:High Mobility Group Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006614:Hindlimb / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D011773:Pyruvates / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
D001786:Blood Glucose; D004396:Coloring Agents; C486328:HBP1 protein, human; D006609:High Mobility Group Proteins; D011773:Pyruvates; D012097:Repressor Proteins; C046522:ethyl pyruvate