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Updated: Mar 3, 2026
The Mouse Stroke Unit Protocol with Standardized Neurological Scoring for Translational Mouse Stroke Studies
Published on: February 7, 2025
Test repositioning for functional assessment of neurological outcome after experimental stroke in mice
Macarena Hernández-Jiménez1,2, Carolina Peña-Martínez1,2, María Del Carmen Godino1,2
1Unidad de Investigación Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Abstract:
Stroke is a cerebrovascular pathology for which the only approved treatment is fibrinolysis. Several studies have focused on the development of new drugs but none has led to effective therapies to date, due, among others, to the difficulty to evaluate clinical deficits in experimental animal models. The present study aims to explore the applicability of known behavioral tests not commonly used in ischemia for the neurological assessment of mice after experimental stroke in different brain areas. A total of 225 CD1 male mice were randomly assigned to permanent middle cerebral artery occlusion by ligature (pMCAO) or permanent anterior cerebral artery occlusion by photothrombosis (pACAO) models. Modified neuroseverity score, footprint test, forced swim test and elevated plus maze were performed. Under these experimental conditions, modified neuroseverity score showed neurological impairment early after experimental stroke in both models. By contrast, the footprint test and the elevated plus maze detected short-term neurological deterioration in the pMCAO model but not in the pACAO model. Furthermore, the forced swim test identified depression-like behavior in mice after ischemia only when the left hemisphere was affected. In conclusion, we propose the repositioning of known neurobehavioral tests, but not commonly used in the stroke field, for the fast detection of neurological impairments early after ischemia, and even specific to discriminate the territory affected by arterial occlusion as well as the hemisphere where brain damage occurs. All these findings may prove useful to improve the experimental design of neuroprotective drugs in order to bridge the gap between experimental studies and clinical trials.
Insights
This study repurposed behavioral tests for early stroke detection in mice. These methods help assess neurological deficits and identify affected brain areas, aiding new drug development.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Animal Models
Background:
- Stroke lacks effective treatments beyond fibrinolysis.
- Evaluating neurological deficits in animal models is challenging.
- New therapeutic strategies require improved preclinical assessment.
Purpose of the Study:
- To evaluate non-traditional behavioral tests for neurological assessment in experimental stroke models.
- To determine the sensitivity of these tests in different stroke models and brain areas.
- To enhance the preclinical evaluation of neuroprotective drugs.
Main Methods:
- 225 male mice underwent permanent middle cerebral artery occlusion (pMCAO) or anterior cerebral artery occlusion (pACAO).
- Neurological deficits were assessed using modified neuroseverity score, footprint test, forced swim test, and elevated plus maze.
- Behavioral tests were analyzed for their ability to detect deficits in distinct stroke models.
Main Results:
- Modified neuroseverity score detected early impairment in both pMCAO and pACAO models.
- Footprint test and elevated plus maze identified short-term deficits in pMCAO but not pACAO.
- Forced swim test revealed depression-like behavior specifically after left-hemisphere ischemia.
Conclusions:
- Repositioned neurobehavioral tests offer rapid detection of early ischemic deficits.
- These tests can discriminate the affected arterial territory and hemisphere.
- Findings can refine experimental designs for neuroprotective drug development, bridging the research-clinical gap.
