doi: 10.1161/01.STR.0000155730.29424.62
(Stroke. 2005;36:530-a.)
© 2005 American Heart Association, Inc.
Letters to the Editor |
Adverse Effects of the Intraluminal Filament Model of Middle Cerebral Artery Occlusion
Department of Anesthesiology
Department of Neurology, University of Regensburg, Regensburg, Germany.
To the Editor:
Animal models of ischemic stroke are of major importance for experimental stroke research. Comprehensive knowledge of the methodological aspects of the different stroke models available is crucial for data interpretation and correlation to human stroke. We therefore appreciate the recent work of Gerriets et al on complications in different models of focal ischemia in rats, taking advantage of high-resolution magnetic resonance imaging (MRI) and magnetic resonance angiography.1
In addition to their findings of subarachnoid hemorrhage and hypothalamic infarction as a cause of hyperthermia, the appearance of ipsilateral masticatory hyperintensities in early MRI associated with temporal muscle necrosis (Figure) has also been identified recently as a complication of the intraluminal filament model of middle cerebral artery occlusion (MCAO). These lesions resulted in impaired body weight evolution and delayed restoration of neurological function in Wistar rats.2 This is neither a laboratory-specific nor a rat strain-specific problem, as can be learned from a publication of Palmer et al.3 Sprague–Dawley rats MRI on day 2 after temporary MCAO (suture technique) depicted extracranial lesions in the temporal muscle that are identical to those found in our laboratory. Unfortunately, the authors do not comment on this finding.
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The cause of the masticatory lesions is yet obscure. Although acute ischemic myopathy caused by transection of the external carotid artery had been discussed,2 further experiments revealed that protection of the external carotid artery was not sufficient to avoid masticatory lesions, and the latter cannot be provoked by transection of the external carotid artery alone (Dittmar MS, Fehm NP, Vatankhah B, unpublished data, 2004). We would be thankful if Gerriets et al could provide information on the presence of masticatory lesions in the rats subjected to MCAO by the 3 different techniques.
We strongly agree on the importance of MRI data in stroke research. Evaluation of different approaches to MCAO in different rat strains by early MRI, not only of intracranial but also of extracranial lesions, is a crucial step to better-understand the pathophysiology of experimental stroke. Ultimately, this may enable us to better-translate animal research into human stroke therapy.
References
1. Gerriets T, Stolz E, Walberer M, Muller C, Rottger C, Kluge A, Kaps M, Fisher M, Bachmann G. Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke. 2004; 35: 2372–2377.
2. Dittmar M, Spruss T, Schuierer G, Horn M. External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats. Stroke. 2003; 34: 2252–2257.
3. Palmer GC, Peeling J, Corbett D, Del Bigio MR, Hudzik TJ. T2-weighted MRI correlates with long-term histopathology, neurology scores, and skilled motor behavior in a rat stroke model. Ann N Y Acad Sci. 2001; 939: 283–296.[Medline] [Order article via Infotrieve]
Response:
Department of Neurology, University Giessen, Germany
Department of Radiology and, Experimental Neurology Research Group, Kerckhoff Klinik Bad Nauheim, Germany
Department of Neurology, University of Massachusetts Medical School, Worcester, Mass
Dittmar et al report ipsilateral temporal muscle necrosis as another important source of potential side effects in rat stroke models. This phenomenon occurred in almost half of the animals subjected to middle cerebral artery occlusion (MCAO) and was related to clinical decline.1 This complication might affect the results of animal stroke studies and thus is of relevance for the transferability of experimental in vivo data to human stroke.
In our recent article, we studied complications and side effects of 3 different rat stroke models: permanent MCAO (suture technique; n=10), 90-minute transient MCAO (suture technique; n=10), and permanent MCAO (macrosphere MCAO; n=10). In this study, male Sprague–Dawley rats (290 to 350 grams) were used.2 We retrospectively re-evaluated T2-weighted magnetic resonance images that were obtained 24 hours after MCAO for the presence of temporal muscle hyperintensities.
In addition, we retrospectively analyzed T2-weighted images of 30 Wistar rats that were similarly subjected to the 3 aforementioned MCAO techniques (unpublished material). All animals were purchased from Harlan Winkelmann, Borchen, Germany.
No muscle lesions could be detected on MRI (Figure) in Wistar rats (n=30) or in Sprague–Dawley rats (n=30).
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Although external carotid artery occlusion was performed in a similar fashion in both laboratories (except for the macrosphere MCAO technique, in which the pterygopalatine artery was ligated), some procedural differences can be noticed.1–3 In our laboratory, we do not use electrocoagulation for vessel dissection that potentially might lead to inadvertent tissue damage. Furthermore, laser Doppler flowmetry was not applied. This technique requires additional incisions close to the origin of the temporal muscle (or within the muscle) that might lead to impairment of collateral blood flow between the left and right external carotid artery territory.
Furthermore, vendor differences could explain the different results between both laboratories, because we purchase our animals from a different breeder. Rat strain and vendor differences in (intracranial) collateral anastomoses have previously been described, so one can speculate whether this could also apply to extracranial collateralization.4 Further studies are warranted for the understanding of extracranial lesions after MCAO.
References
1. Dittmar M, Spruss T, Schuierer G, Horn M. External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats. Stroke. 2003; 34: 2252–2257.
2. Gerriets T, Stolz E, Walberer M, Muller C, Rottger C, Kluge A, Kaps M, Fisher M, Bachmann G. Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke. 2004; 35: 2372–2377.
3. Gerriets T, Li F, Silva MD, Meng X, Brevard M, Sotak CH, Fisher M. The macrosphere model. Evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats. J Neurosci Methods. 2003; 122: 201–211.[CrossRef][Medline] [Order article via Infotrieve]
4. Oliff HS, Coyle P, Weber E. Rat strain and vendor differences in collateral anastomoses. J Cereb Blood Flow Metab. 1997; 17: 571–576.[CrossRef][Medline] [Order article via Infotrieve]
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