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Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats
Published on: April 21, 2017
Rat middle cerebral artery occlusion: correlations between histopathology, T2-weighted magnetic resonance imaging,
J Peeling1, D Corbett, M R Del Bigio
1Department of Pharmacology and Therapeutics and Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
Abstract:
During attempts to develop the intraluminal suture model of transient middle cerebral artery occlusion (MCAO) in the Sprague Dawley strain of rats, we noticed a wide variability in lesion size seen with T2-weighed magnetic resonance imaging (MRI) or histopathology, as well as in scores for behavioral indices. It was our intent to examine the results of the study carefully and determine whether there were strong point-to-point correlations between the degree of lesion size determined from T2-weighted MRI or histopathology and intermediate or long-term neurologic/behavioral assessments. Baseline behavioral scores for forelimb dexterity (staircase test) were obtained on all animals in the period before receiving 60 minutes of transient MCAO. After MCAO, animals were tested at specified intervals from 1 to 21 days for composite neurologic deficits. T2-weighted MRI was taken at 2 and 7 days post-MCAO. At 30 and 60 days post-MCAO, animals were retested in the staircase test with subsequent histopathologic examination of the brains. Indeed, there were highly significant correlations between lesion size determined by MRI and histopathology. The damage observed in the T2-weighted MRI, as well as the size of the histopathologic lesions, were in turn highly correlated to deficiencies observed in the composite neurologic assessments, as well as to deficits at 30 and 60 days post-MCAO for skilled use of the contralateral forepaw (damaged side). In the latter test, the correlations were somewhat less significant for the ability of rats to reach for food with the ipsilateral forepaw (undamaged side).
Insights
This study found strong correlations between stroke lesion size in rats and long-term behavioral deficits. Accurately measuring stroke damage using MRI and histopathology predicts functional recovery after middle cerebral artery occlusion.
Area of Science:
- Neuroscience
- Medical Imaging
- Animal Models
Background:
- Transient middle cerebral artery occlusion (MCAO) models in rats often show variable lesion sizes.
- Accurate assessment of stroke-induced brain damage and its correlation with functional deficits is crucial for research.
Purpose of the Study:
- To investigate the correlation between lesion size determined by T2-weighted MRI and histopathology.
- To determine the relationship between stroke lesion size and intermediate/long-term neurological and behavioral assessments in a rat model.
Main Methods:
- Developed an intraluminal suture model of transient middle cerebral artery occlusion (MCAO) in Sprague Dawley rats.
- Assessed forelimb dexterity using the staircase test before MCAO and at 30 and 60 days post-MCAO.
- Evaluated composite neurological deficits from 1 to 21 days post-MCAO.
- Utilized T2-weighted MRI at 2 and 7 days post-MCAO.
- Conducted histopathological examination of brain tissue at 60 days post-MCAO.
Main Results:
- Highly significant correlations were found between lesion size measured by MRI and histopathology.
- Both MRI-derived and histopathological lesion sizes strongly correlated with composite neurological deficits.
- Significant correlations were observed between lesion size and deficits in skilled use of the contralateral forepaw (damaged side) at 30 and 60 days post-MCAO.
- Correlations were less significant for the ipsilateral forepaw (undamaged side) reaching ability.
Conclusions:
- T2-weighted MRI and histopathology provide reliable measures of stroke lesion size in the MCAO rat model.
- Stroke lesion size is a strong predictor of both acute and long-term functional neurological deficits.
- This validates the use of quantitative lesion assessment for evaluating stroke severity and recovery in preclinical research.

