A mouse model of ischemic spinal cord injury with delayed paralysis caused by aortic cross-clamping.
BACKGROUND
Spinal cord ischemia and paralysis are devastating perioperative complications that can accompany open or endovascular repair surgery for aortic aneurysms. Here, we report on the development of a new mouse model of spinal cord ischemia with delayed paralysis induced by cross-clamping the descending aorta.


METHODS
Transient aortic occlusion was produced in mice by cross-clamping the descending aorta through a lateral thoracotomy. To establish an optimal surgical procedure with limited mortality, variable cross-clamp times and core temperatures were tested between experiments.


RESULTS
The onset of paresis or paralysis and postsurgical mortality varied as a function of cross-clamp time and core temperature that was maintained during the period of cross-clamp. Using optimal surgical parameters (7.5-min cross-clamp duration at 33°C core temperature), the onset of paralysis is delayed 24-36 h after reperfusion, and more than 95% of mice survive through 9 weeks after surgery. These mice are further stratified into two groups, 70% (n = 19/27) of mice developing severe hind limb paralysis and the remaining mice showing mild, though still permanent, behavioral deficits.


CONCLUSIONS
This new model should prove useful as a preclinical tool for screening neuroprotective therapeutics and for defining the basic biologic mechanisms that cause delayed paralysis and neurodegeneration after transient spinal cord ischemia.
Awad
Hamdy
H
Department of Anesthesiology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Ankeny
Daniel P
DP
Guan
Zhen
Z
Wei
Ping
P
McTigue
Dana M
DM
Popovich
Phillip G
PG
D000136:Acid-Base Equilibrium / Q000502:physiology; D000758:Anesthesia; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D001784:Blood Gas Analysis; D003250:Constriction; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010243:Paralysis / Q000209:etiology* / Q000523:psychology; D011182:Postoperative Care; D015427:Reperfusion Injury; D020760:Spinal Cord Ischemia / Q000209:etiology* / Q000473:pathology* / Q000523:psychology; D013348:Subclavian Artery / Q000502:physiology; D013525:Surgical Instruments / Q000009:adverse effects
Stroke. 1980 Mar-Apr;11(2):200-2
7368250
J Vasc Surg. 1994 Aug;20(2):255-62
8040949
Stroke. 2000 Jan;31(1):208-13
10625739
Ann Thorac Surg. 2007 Apr;83(4):1345-55; discussion 1355
17383338
Acta Biol Hung. 1989;40(3):229-35
2561246
J Surg Res. 2007 Jul;141(1):78-82
17512544
Eur J Cardiothorac Surg. 2004 May;25(5):708-15
15082271
Ann Surg. 2002 Oct;236(4):471-9; discussion 479
12368676
J Vasc Surg. 1991 Mar;13(3):355-65
1999854
Exp Neurol. 2008 Aug;212(2):275-84
18511046
Circulation. 2008 Aug 19;118(8):808-17
18678769
Anesth Analg. 2003 Jun;96(6):1777-1784
12761011
Exp Neurol. 2004 Nov;190(1):17-31
15473977
Spine J. 2008 Nov-Dec;8(6):859-74
18329959
Arch Surg. 2003 Feb;138(2):175-9; discussion 180
12578415
J Neurosci. 2000 Sep 15;20(18):6879-87
10995832
J Vasc Surg. 1987 Oct;6(4):383-90
3656586
Surg Annu. 1987;19:41-65
3547716
Am J Surg. 2009 Aug;198(2):250-5
19268911
Epilepsy Res. 2008 Dec;82(2-3):219-22
18804344
J Comp Neurol. 2003 Jul 21;462(2):223-40
12794745
J Neurotrauma. 2009 Mar;26(3):333-40
19292695
J Neurotrauma. 2006 May;23(5):635-59
16689667
Stroke. 1994 Oct;25(10):2038-46
8091450
J Am Coll Surg. 2006 Jul;203(1):44-53
16798486
Eur J Vasc Endovasc Surg. 2009 Jun;37(6):654-60
19359200
Epilepsia. 2008 Feb;49(2):248-55
17941842
J Clin Invest. 2009 Oct;119(10):2990-9
19770513
J Vasc Surg. 2005 Jan;41(1):99-107
15696051
J Neurotrauma. 2009 Mar;26(3):301-12
19245308
Surgeon. 2005 Dec;3(6):396-405
16353860
Int J Neurosci. 2005 Aug;115(8):1239-44
16040365