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Model development and behavioral assessment of focal cerebral ischemia in rats
Abstract:
Stroke in humans is usually focal and occurs in the Middle Cerebral Artery (MCA) distribution. There are several rat models that mimic strokes clinically seen in human. Severity of ischemia can be determined by occlusion time, arteries occluded i.e. MCA alone or combined with one or both Common Carotid Arteries (CCA), and/or location of the occlusion. In this study three focal cerebral infarctions (stroke) were induced for 90 and 120 minutes due to the occlusion of: the MCA alone (MCAo); MCA plus unilateral CCA (MCAo+1CCAo); and MCA plus bilateral CCA (MCAo+2CCAo). Histological parameters included infarct lesion size and hemispheric swelling. Since functional recovery of clinical deficits in stroke often correlates with the efficacy of anti-ischemic therapy, we focused on the behavioral recovery. We combined many sources to obtain comprehensive guidelines for clinical behavior evaluation. Tests included limb flexion, torso twisting, circling, lateral push resistance, beam balancing and walking, hindlimb placing, and inverted angle-board gripping. Occlusion lasting 90 minutes was found to have consistent and repeatable deficits. Results from our study demonstrate 120 minutes of occlusion produced a 60% morality rate and was therefore dropped. Body weight changes between groups showed that increased occlusion time produced more weight loss. Behavior changes indicated that MCAo+2CCAo for 90 minutes demonstrated assessable and consistent clinical deficits for the screening of potential therapeutics.
Insights
This study refined rat stroke models by testing Middle Cerebral Artery occlusion durations and combinations with carotid arteries. The MCAo+2CCAo model for 90 minutes showed consistent deficits for testing stroke therapeutics.
Area of Science:
- Neuroscience
- Ischemic Stroke Research
- Animal Models of Disease
Background:
- Human stroke often affects the Middle Cerebral Artery (MCA) distribution.
- Rat models are crucial for studying focal cerebral ischemia and evaluating therapeutic strategies.
- Stroke severity is influenced by occlusion duration and affected arteries.
Purpose of the Study:
- To establish reliable rat models of focal cerebral infarction.
- To evaluate the impact of different occlusion methods (MCA alone, MCA+CCA) and durations on stroke severity and behavioral deficits.
- To identify an optimal model for screening anti-ischemic therapies.
Main Methods:
- Induction of focal cerebral infarction in rats via Middle Cerebral Artery occlusion (MCAo) alone, MCAo plus unilateral Common Carotid Artery occlusion (MCAo+1CCAo), and MCAo plus bilateral CCA occlusion (MCAo+2CCAo) for 90 and 120 minutes.
- Assessment of histological parameters including infarct lesion size and hemispheric swelling.
- Comprehensive behavioral evaluation using tests for limb function, motor coordination, balance, and neurological deficits.
Main Results:
- A 120-minute occlusion period resulted in a 60% mortality rate, leading to its discontinuation.
- Ninety-minute occlusions produced consistent and repeatable neurological deficits.
- The MCAo+2CCAo model for 90 minutes demonstrated significant and consistent behavioral deficits, suitable for therapeutic screening.
- Increased occlusion time correlated with greater body weight loss.
Conclusions:
- The 90-minute MCAo+2CCAo rat model provides a reliable and reproducible method for inducing focal cerebral ischemia.
- This model is effective for assessing behavioral deficits and screening potential therapeutics for stroke.
- Optimizing stroke models is critical for advancing the development of effective anti-ischemic therapies.