title: Minimally invasive neuroradiologic model of preclinical transient middle cerebral artery occlusion in canines.
abstract: Stroke is currently the third leading cause of death in the United States, with approximately 780,000 Americans affected by a new or recurring stroke each year. Although a variety of therapeutic approaches have shown promise in small-animal models of stroke, the vast majority of clinical trials to test the efficacy of such modalities have failed. To bridge the translational gap between laboratory and clinical research, we developed a preclinical model of acute ischemic stroke in dogs. Using a minimally invasive endovascular approach, a platinum coil was intravascularly guided through the vertebrobasilar system under C-arm fluoroscopy to occlude the M1 segment of the middle cerebral artery (MCA) for 1 h. The approach included femoral artery catheterization to access the MCA and therefore eliminated the occurrence of head trauma associated with other preclinical stroke models relying on transorbital or craniectomy approaches. After 1 h of focal MCA ischemia, the coil was retrieved to cause reperfusion, which was verified by arteriograms. At 24 h, T2-weighted coronal magnetic resonance (MR) images were acquired and processed for three-dimensional reconstruction of the brain and its vasculature. Infarction, limited to the area at risk, was noted. Two independent observers calculated the mean percentage hemispherical lesion volumes as follows: observer 1, 30.9 +/- 2.1%; observer 2, 31.2 +/- 4.3%. Infarct-affected changes in histology were determined by hematoxylin and eosin as well as by Fluoro-Jade staining. This work reports the successful development of a powerful preclinical model of stroke that lends itself to the study of biologic mechanisms as well as to testing experimental therapeutics.
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Rink
authors.forename: Greg
authors.initials: G
authors.lastname: Christoforidis
authors.forename: Amir
authors.initials: A
authors.lastname: Abduljalil
authors.forename: Marinos
authors.initials: M
authors.lastname: Kontzialis
authors.forename: Valerie
authors.initials: V
authors.lastname: Bergdall
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.forename: Andrew
authors.initials: A
authors.lastname: Slivka
authors.forename: Michael
authors.initials: M
authors.lastname: Knopp
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D011859:Radiography
references.citation: J Trauma. 2007 Mar;62(3):777-8
references.pmid: 17414367
references.citation: Stroke. 1992 Apr;23(4):552-9
references.pmid: 1561688
references.citation: Altern Lab Anim. 2005 Oct;33(5):519-27
references.pmid: 16268763
references.citation: J Neurosci Methods. 2003 Jan 30;122(2):201-11
references.pmid: 12573479
references.citation: Stroke. 1997 Mar;28(3):632-7; discussion 637-8
references.pmid: 9056623
references.citation: Contemp Top Lab Anim Sci. 2000 Jan;39(1):14-6
references.pmid: 11178309
references.citation: Lab Anim Sci. 1991 Aug;41(4):372-7
references.pmid: 1658487
references.citation: Brain Res. 1997 Dec 5;778(1):16-24
references.pmid: 9462873
references.citation: Stroke. 2005 Oct;36(10):2258-64
references.pmid: 16166580
references.citation: Stroke. 1997 Feb;28(2):419-26; discussion 426-7
references.pmid: 9040700
references.citation: Stroke. 1998 Sep;29(9):1912-6
references.pmid: 9731618
references.citation: J Med Primatol. 2007 Dec;36(6):375-80
references.pmid: 17976043
references.citation: J Cereb Blood Flow Metab. 2008 Apr;28(4):786-96
references.pmid: 18000514
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5621-6
references.pmid: 10792049
references.citation: AJNR Am J Neuroradiol. 2008 Apr;29(4):745-52
references.pmid: 18202238
references.citation: J Neurotrauma. 2005 Jun;22(6):623-8
references.pmid: 15941372
references.citation: Stroke. 1996 Sep;27(9):1616-22; discussion 1623
references.pmid: 8784138
references.citation: Stroke. 2007 Jan;38(1):138-45
references.pmid: 17122422
references.citation: Stroke. 1998 Oct;29(10):2162-70
references.pmid: 9756599
references.citation: Circulation. 2008 Jan 29;117(4):e25-146
references.pmid: 18086926
references.citation: Stroke. 2004 Oct;35(10):2372-7
references.pmid: 15345802
references.citation: Stroke. 2001 Jun;32(6):1349-59
references.pmid: 11387498
references.citation: Stroke. 1989 Jan;20(1):84-91
references.pmid: 2643202
references.citation: Brain Res. 1997 Mar 14;751(1):37-46
references.pmid: 9098566
references.citation: Stroke. 1995 Apr;26(4):627-34; discussion 635
references.pmid: 7709410
references.citation: Stat Methods Med Res. 1999 Jun;8(2):135-60
references.pmid: 10501650
references.citation: J Stroke Cerebrovasc Dis. 2006 Sep-Oct;15(5):202-8
references.pmid: 17904076
references.citation: J Med Ethics. 2007 Nov;33(11):655-8
references.pmid: 17971469
references.citation: Stroke. 2000 Dec;31(12):3054-63
references.pmid: 11108772
references.citation: Surg Neurol. 1994 May;41(5):368-73
references.pmid: 8009410
references.citation: Stroke. 1970 Nov-Dec;1(6):439-48
references.pmid: 5001842
references.citation: Yakubutsu Seishin Kodo. 1993 Feb;13(1):9-17
references.pmid: 8317177
references.citation: Acta Neurochir (Wien). 1991;109(3-4):126-32
references.pmid: 1858530
references.citation: ILAR J. 2003;44(2):85-95
references.pmid: 12652003