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Published on: July 21, 2013
Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model
Adam J Wells1, Robert Vink2, Stephen C Helps3
1Adelaide Centre for Neuroscience Research, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia; Department of Neurosurgery, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.
Introduction:
Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model.
Materials And Methods:
30 adult female Merino sheep (n = 8-12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed.
Results:
No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%.
Conclusions:
Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies.
Insights
Permanent middle cerebral artery occlusion in sheep causes severe edema, increased intracranial pressure, and mortality, mimicking human stroke. This ovine model is valuable for testing new stroke therapies.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- Malignant middle cerebral artery (MCA) stroke leads to high mortality due to cerebral edema.
- Rodent models show poor clinical translation for anti-edema therapies.
- Large animal models are needed for stroke research.
Purpose of the Study:
- To characterize the intracranial pressure (ICP) response to MCA occlusion in an ovine stroke model.
- To evaluate the potential of an ovine model for studying malignant MCA stroke.
Main Methods:
- 30 adult female Merino sheep underwent sham surgery, temporary, or permanent MCA occlusion.
- Intracranial pressure (ICP) and brain tissue oxygen were monitored for 24 hours.
- MRI, triphenyltetrazolium chloride (TTC) staining for infarct volume, and histology were performed.
Main Results:
- Temporary MCA occlusion showed ischemia without significant edema or ICP increase.
- Permanent MCA occlusion led to significantly elevated ICP, space-occupying edema, and 30% mortality.
- TTC infarct volumes were 7.9+/-5.1% for temporary and 27.4+/-6.4% for permanent occlusion.
Conclusions:
- Permanent proximal MCA occlusion in sheep accurately models malignant MCA stroke.
- The ovine model demonstrates space-occupying edema, raised ICP, and mortality comparable to human stroke.
- This model is suitable for pre-clinical testing of anti-edema therapies.
