Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats
Nagesh C Shanbhag1,2, Robert H Henning2, Lothar Schilling1
1Division of Neurosurgical Research, Medical Faculty Mannheim, Heidelberg University, Mannheim, D-68167, Germany.
Abstract:
Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients.
Insights
A novel bowling pin-tipped filament significantly reduces mortality and brain damage in rat stroke models. This improved method for middle cerebral artery occlusion offers better survival and mimics human stroke progression.
Area of Science:
- Neuroscience
- Ischemic Stroke Research
- Animal Models of Stroke
Background:
- Intraluminal filament occlusion of the middle cerebral artery (MCA) is a standard method for studying focal brain ischemia in rats.
- Permanent MCA occlusion models often result in high mortality rates, limiting their utility.
- Existing filament designs can cause vascular distortion and extensive damage.
Purpose of the Study:
- To develop and evaluate a novel intraluminal filament with a bowling pin-shaped tip (BP-tip) for permanent MCA occlusion.
- To compare the efficacy and safety of the BP-tip filament against conventional filaments in a rat stroke model.
- To assess the impact of the BP-tip filament on mortality, ischemic damage, and collateral flow.
Main Methods:
- Male Sprague-Dawley rats underwent permanent MCA occlusion using either BP-tip or conventional filaments.
- Ischemic damage and swelling were quantified using silver nitrate staining.
- Collateral flow was assessed via selective dye perfusion of the internal carotid artery.
Main Results:
- The BP-tip filament significantly reduced mortality from 60% to 12.5% compared to conventional filaments.
- BP-tip occlusion resulted in significantly smaller ischemic damage (p < 0.05) and spared the occipital region and hypothalamus.
- BP-tip filaments did not induce vascular distortion, unlike conventional filaments, and showed improved collateral filling of the posterior cerebral artery territory.
Conclusions:
- The BP-tip filament offers superior survival rates in permanent MCA occlusion models.
- This novel filament design effectively mimics the course of malignant stroke in patients while minimizing procedural complications.
- The BP-tip filament represents a significant advancement for stroke research, enabling more reliable and reproducible studies of focal brain ischemia.
