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Published on: April 19, 2011
Pattern of time-dependent reduction of histologically determined infarct volume after focal ischaemia in mice
Petra Henrich-Noack1, Kathrin Baldauf, Georg Reiser
1Leibniz Institute for Neurobiology, Brennecke Str. 6, 39118 Magdeburg, Germany. phnoack@gmail.com
Abstract:
The mouse model of transcranial permanent occlusion of the middle cerebral artery (tpMCAO) is widely used in stroke research. Here we quantified infarct size using a conventional histological method at several post-ischaemic times, going beyond the commonly analysed period of up to 2 days, following artery occlusion. Two different mouse strains, which are widely used for pharmacological studies of neuroprotection and for genetic engineering, were used. A drill whole was made into the skull of anaesthetised mice and ischaemia was induced by electrocoagulation of the middle cerebral artery. In both mouse strains tested (C57Black/6 and NMRI), the measured infarct volumes decreased significantly during the first days after tpMCAO. Notably, 13 days after surgery, ischaemic and sham-operated animals had indistinguishably small lesions, which where in the range of only 5% of the infarct size on day 2 post-ischaemia. The standard method of calculating oedema and shrinkage correction provided no sufficient explanation for this significant decrease in infarct volume. There was, however, evidence that structural changes in the residual ipsilateral hemisphere may compromise the significance of results arising from the method of calculating oedema and shrinkage correction. In conclusion, our study indicates that the pronounced and fast, time-dependent decrease in histologically defined infarct volume can compromise results when studying the lasting neuroprotective effects of potential drugs.
Insights
Stroke research using the mouse model of permanent middle cerebral artery occlusion (tpMCAO) shows infarcts shrink significantly over time. This rapid volume reduction challenges assessments of long-term neuroprotective drug efficacy.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- The permanent middle cerebral artery occlusion (tpMCAO) model is crucial for stroke research.
- Histological infarct quantification is standard, but typically limited to early time points post-stroke.
Purpose of the Study:
- To quantify infarct size over an extended period in the tpMCAO mouse model.
- To evaluate the impact of infarct volume changes on assessing neuroprotective therapies.
Main Methods:
- Induced ischemia via electrocoagulation of the middle cerebral artery in C57Black/6 and NMRI mice.
- Utilized conventional histological methods for infarct volume quantification at multiple time points.
- Analyzed infarct size beyond the typical 2-day post-ischemia period.
Main Results:
- Significant decrease in infarct volume observed in both mouse strains within days of tpMCAO.
- By day 13, infarcts were minimal (approx. 5% of day 2 size) and comparable to sham controls.
- Standard edema and shrinkage correction methods did not fully explain the observed infarct volume reduction.
Conclusions:
- The rapid, time-dependent decrease in infarct volume can confound the evaluation of sustained neuroprotective effects.
- Structural changes in the brain hemisphere may affect the reliability of standard correction methods.
- Results highlight the need for careful consideration of time points in stroke drug efficacy studies using the tpMCAO model.

