Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke

Abstract

Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone-coated nylon suture were studied over 7 days in Sprague-Dawley rats (n = 36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone-coated suture (e.g. total cerebral infarct volume at 24 h before any fatalities was 119.9 +/- 79.8 mm3, cf. 183.0 +/- 36.5 mm3, n = 12 for each, P < 0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone-coated suture was further studied in Wistar and Fischer-344 rats (n = 12 for each). Seventy-five per cent of the Wistar's died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer-344 rats were both significantly greater compared with Sprague-Dawley rats (e.g. total cerebral infarct volume at 24 h in the former was 253.6 +/- 25.4 mm3, n = 11, P < 0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone-coated suture and the Fischer-344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.

Experimental stroke: ischaemic lesion volume and oedema formation differ among rat strains (a comparison between Wistar and Sprague–Dawley rats using MRI)

“…This might explain the considerable variability of results reported from different laboratories using similar MCAO techniques in rats (Coyle & Jokelainen 1982, Aspey et al 1998. In the present study, Sprague-Dawley and Wistar rats reacted differently to permanent and transient MCAO with respect to ischaemic lesion volume and oedema formation.…”

“…Several studies have reported differences in the extent of ischaemic lesion volumes among rat strains (Duverger & MacKenzie 1988, Markgraf et al 1993, Oliff et al 1995a,b, 1996, Sauter & Rudin 1995, Aspey et al 1998, Ren et al 2004. However, the effect of reperfusion on ischaemic lesion volume and oedema formation in consideration of rat strain differences has not been investigated systematically.…”

Edaravone Protects against Hypoxia/Ischemia-Induced Endoplasmic Reticulum Dysfunction

“…An image analysis system (NIH 1.61 software) was used to determine the infracted volume (MV), right hemisphere volume (RV), and left hemisphere volume (LV). To compensate for the effect of brain edema on the measured infarct volume in the ischemic hemisphere, the infarct volume in each mouse was corrected as described (Swanson et al, 1990;Aspey et al, 1998) with the following formula. Corrected infarct volume (%) ϭ [LV Ϫ (RV Ϫ MV)]/LV ϫ 100.…”

Differences in Ischemic Lesion Evolution in Different Rat Strains Using Diffusion and Perfusion Imaging

“…The intraluminal suture occlusion of the middle cerebral artery (MCAO) in rats is one of the most widely used models to study focal cerebral ischemia. However, considerable variability in the extent of final infarct size have been recurrent findings with this model 1,2 and compromised its potential in preclinical therapeutic assessments. This may be explained by a number of factors, including differences in anesthesia, in size and type of filament used, and modifications of the technique.…”