Complications and Pitfalls in Rat Stroke Models for Middle Cerebral Artery Occlusion

Abstract

Background and Purpose-Investigating focal cerebral ischemia requires animal models that are relevant to human stroke.Complications and side effects are common among these models. The present study describes potential pitfalls in 3 techniques for middle cerebral artery occlusion (MCAO) in rats using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Methods-Rats were subjected to temporary MCAO for 90 minutes using the suture technique (group I; nϭ10) or to permanent MCAO using the suture technique (group II; nϭ10) or the macrosphere technique (group III; nϭ10). Clinical evaluation was performed after 3 hours and 24 hours. After 24 hours, animals underwent MRI and MRA to determine lesion size and the intracranial vascular status. Results-Hemispheric lesion volume was significantly smaller in group I (14.6%) compared with groups II (35.2%; PϽ0.01) and III (21.3%; PϽ0.05). Two animals (1 each in group II and III) did not demonstrate neurological deficits and had no lesion on MRI and a patent MCA main stem on MRA. Subarachnoid hemorrhage was detected in 2 animals (1 each in group I and II). MRA indicated a patent MCA main stem in 2 animals (group II), although both rats displayed neurological deficits. Hypothalamic infarction with subsequent pathological hyperthermia was detected in all animals in group II and in 1 rat in group III. Conclusions-Model failures occurred frequently in all groups. MRI and MRA helps to identify animals that need to be excluded from experimental stroke studies.

Manganese-Enhanced MRI of Brain Plasticity in Relation to Functional Recovery after Experimental Stroke

“…of T 2 in contralateral tissue. The edema-corrected hemispheric lesion volume (%HLV e ) was calculated as described by Gerriets et al (2004):…”

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

“…The most common model of MCAO in the rodent is the intraluminal filament technique, and model failure is a potential pitfall of this technique (Dittmar et al, 2005). Magnetic resonance angiography has been used to identify and exclude these animals earlier (Gerriets et al, 2004). Although use of MRA is limited in the experimental setting, development of new contrast agents for examination of atherosclerotic plaques can be tested easily.…”

Tocotrienol Vitamin E Protects against Preclinical Canine Ischemic Stroke by Inducing Arteriogenesis

“…As a result, rodent stroke models have been criticized for the anatomical disparity between small and large mammalian brains, large variability in infarct volumes, and inaccurate methods of inducing and confirming arterial occlusion (Gerriets et al, 2004). These considerations develop a compelling rationale to engage a translational relevant preclinical approach to test the therapeutic efficacy of TE natural vitamin E (Rink et al, 2008).…”