title: Development of a simplified spinal cord ischemia model in mice.
abstract: Use of genetically manipulated mice facilitates understanding pathological mechanisms in many diseases and contributes to therapy development. However, there is no practical and clinically relevant mouse model available for spinal cord ischemia. This report introduces a simplified long-term outcome mouse model of spinal cord ischemia. Male C57Bl/6J mice were anesthetized with isoflurane and endotracheally intubated. The middle segment of the thoracic aorta was clamped for 0, 8, 10 or 12 min via left lateral thoracotomy. Rectal temperature was maintained at 37.0+/-0.5 degrees C. A laser Doppler probe was used to measure lumbar spinal cord blood flow during thoracic aorta cross-clamping. Open field locomotor function and rotarod performance were evaluated at 1h and 1, 3, 5, and 7 days post-injury. Surviving neurons in the lumbar ventral horn were counted at 7 days post-injury. Cross-clamping the middle segment of the thoracic aorta resulted in approximately 90% blood flow reduction in the lumbar spinal cord. Neurological deficit and neuronal cell death were associated with ischemia duration. Another set of mice were subjected to 10 min aortic clamping or sham surgery and neurological function was examined at 1h and 1, 3, 5, 7, 14, and 28 days. Four of 5 mice (80%) in the injured group survived 28 days and had significant neurological deficit. This study indicates that cross-clamping of the aorta via left thoracotomy is a simple and reliable method to induce spinal cord ischemia in mice allowing definition of long-term outcome.
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Britz
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Lombard
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D016923:Cell Death; D004195:Disease Models, Animal; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D011897:Random Allocation; D012039:Regional Blood Flow; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000473:pathology; D013525:Surgical Instruments; D013908:Thoracotomy / Q000379:methods; D013997:Time Factors
references.citation: Exp Neurol. 1996 Jun;139(2):244-56
references.pmid: 8654527
references.citation: Stroke. 2000 Jan;31(1):208-13
references.pmid: 10625739
references.citation: Stroke. 1996 Oct;27(10):1850-8
references.pmid: 8841344
references.citation: J Vasc Surg. 1993 Feb;17(2):357-68; discussion 368-70
references.pmid: 8433431
references.citation: Behav Neurosci. 2006 Aug;120(4):826-34
references.pmid: 16893288
references.citation: J Spinal Disord. 1994 Aug;7(4):285-95
references.pmid: 7949696
references.citation: Spinal Cord. 2005 Mar;43(3):162-6
references.pmid: 15570318
references.citation: Vasc Endovascular Surg. 2009 Oct-Nov;43(5):444-51
references.pmid: 19640911
references.citation: Ann Surg. 2003 Sep;238(3):372-80; discussion 380-1
references.pmid: 14501503
references.citation: Eur J Vasc Endovasc Surg. 2009 Jun;37(6):640-5
references.pmid: 19362499
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3513-8
references.pmid: 11248109
references.citation: Neurosci Res. 2007 Jan;57(1):148-56
references.pmid: 17083989
references.citation: J Vasc Surg. 1997 Oct;26(4):616-22
references.pmid: 9357462
references.citation: Exp Neurol. 2009 Apr;216(2):365-74
references.pmid: 19150614
references.citation: J Neurotrauma. 2002 Feb;19(2):205-21
references.pmid: 11893023
references.citation: J Vasc Surg. 2002 Apr;35(4):631-9
references.pmid: 11932655
references.citation: J Vasc Surg. 2006 Dec;44(6):1188-97
references.pmid: 17145420
references.citation: Annu Rev Neurosci. 2001;24:807-43
references.pmid: 11520919
references.citation: Neurobiol Dis. 2006 Jun;22(3):694-701
references.pmid: 16545959
references.citation: J Cereb Blood Flow Metab. 1994 May;14(3):526-35
references.pmid: 8163596
references.citation: Spinal Cord. 2007 May;45(5):367-79
references.pmid: 16955071
references.citation: Anaesthesist. 2008 Oct;57(10):988-97
references.pmid: 18604508
references.citation: Spinal Cord. 2006 Mar;44(3):182-7
references.pmid: 16130019
references.citation: J Vasc Surg. 2000 Jun;31(6):1093-102
references.pmid: 10842145
references.citation: Am J Surg. 2009 Aug;198(2):250-5
references.pmid: 19268911
references.citation: Ann Thorac Surg. 1997 Nov;64(5):1279-85; discussion 1286
references.pmid: 9386691
references.citation: J Vasc Surg. 2005 Jan;41(1):99-107
references.pmid: 15696051
references.citation: J Endovasc Ther. 2000 Apr;7(2):132-5
references.pmid: 10821099