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Systematic review of survival time in experimental mouse stroke with impact on reliability of infarct estimation
Carina Kirstine Klarskov1, Mikkel Buster Klarskov1, Henrik Hasseldam1
1University of Copenhagen, Faculty of Health and Medical Sciences-Department of Biomedicine, BRIC, Københavns Biocenter, Ole Maaloes vej 5, Copenhagen 2200-N, Denmark.
Background:
Stroke is the second most common cause of death worldwide. Only one treatment for acute ischemic stroke is currently available, thrombolysis with rt-PA, but it is limited in its use. Many efforts have been invested in order to find additive treatments, without success. A multitude of reasons for the translational problems from mouse experimental stroke to clinical trials probably exists, including infarct size estimations around the peak time of edema formation. Furthermore, edema is a more prominent feature of stroke in mice than in humans, because of the tendency to produce larger infarcts with more substantial edema.
Purpose:
This paper will give an overview of previous studies of experimental mouse stroke, and correlate survival time to peak time of edema formation. Furthermore, investigations of whether the included studies corrected the infarct measurements for edema and a comparison of correction methods will be discussed.
Method:
Relevant terms were searched in the National Library of Medicine PubMed database. A method for classification of infarct measurement methods was made using a naming convention.
Conclusion:
Our study shows that infarct size estimations are often performed around the peak time of edema, with a median of 24h. Most studies do consider edema formation, however, there is no consensus on what method to use to correct for edema. Furthermore, investigations into neuroprotective drugs should use longer survival times to ensure completion of the investigated process. Our findings indicate a need for more research in this area, and establishment of common correction methodology.
Insights
Estimating stroke infarct size in mice is challenging due to edema. Studies often measure infarcts at peak edema, but lack a standard method for correction, hindering translation to human stroke treatments.
Area of Science:
- Neurology
- Experimental Medicine
- Biomedical Research
Background:
- Stroke is a leading global cause of death, with limited acute treatments.
- Current research faces challenges in translating experimental stroke findings to clinical trials.
- Edema formation significantly impacts infarct size estimation in mouse models of stroke.
Purpose of the Study:
- To review experimental mouse stroke studies and correlate survival time with peak edema.
- To assess if studies corrected infarct measurements for edema.
- To compare different methods used for edema correction in stroke research.
Main Methods:
- A systematic literature search was conducted using PubMed.
- Studies were analyzed for infarct measurement and edema correction methodologies.
- A classification system was developed for infarct measurement techniques.
Main Results:
- Infarct size estimations in mouse stroke models are frequently performed around 24 hours, coinciding with peak edema.
- While most studies acknowledge edema, there is no consensus on correction methods.
- Significant differences exist in how edema impacts infarct measurements across studies.
Conclusions:
- Standardization of edema correction methods is crucial for reliable infarct size estimation in experimental stroke.
- Future research should utilize longer survival times to better assess neuroprotective effects.
- Addressing methodological inconsistencies will improve the translational validity of mouse stroke models.
