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Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke
1Reta Lila Weston Institute of Neurological Studies, UCL Medical School, London, UK.
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.
Insights
This study optimized the middle cerebral artery occlusion (MCAO) rat model for stroke research. Combining silicone-coated sutures with Fischer-344 rats yielded the most consistent and reliable results for acute stroke modeling.
Area of Science:
- Neuroscience
- Animal Models
- Stroke Research
Background:
- Variability in middle cerebral artery occlusion (MCAO) rat models hinders research.
- Standardizing MCAO models is crucial for reliable stroke studies.
Purpose of the Study:
- To systematically investigate suture type and rat strain effects on MCAO model outcomes.
- To identify a combination that provides consistent and reliable results for acute stroke modeling.
Main Methods:
- Compared uncoated and silicone-coated sutures in Sprague-Dawley rats over 7 days.
- Evaluated silicone-coated sutures in Wistar and Fischer-344 rats.
- Assessed clinical outcomes, neuropathology, infarct volume, mortality, and motor deficits.
Main Results:
- Silicone-coated sutures resulted in less severe but more variable outcomes than uncoated sutures in Sprague-Dawley rats.
- Wistar rats showed high mortality due to edema with silicone-coated sutures.
- Fischer-344 rats exhibited significantly greater infarcts and motor deficits, with high consistency (CV=10.0%) using silicone-coated sutures.
Conclusions:
- The combination of silicone-coated sutures and Fischer-344 rats provides a highly consistent and reliable acute stroke model.
- This optimized model can advance preclinical stroke research.