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Qualitative and quantitative analysis of the progressive cerebral damage after middle cerebral artery occlusion in
C Chiamulera1, A Terron, A Reggiani
1Glaxo Research Laboratories, Verona, Italy.
Abstract:
The middle cerebral artery occlusion (MCAO) in mice induces a focal cerebral ischaemia at the level of the tempo-parietal cortex. Histological staining and immunohistochemical markers were used to characterize the temporal progression of the cerebral infarct: both qualitative and quantitative analyses were performed at different days after the MCAO. At 3 days after MCAO, an extensive necrosis of the cerebral parenchyma was accompanied by extravasation and by massive oedema. After 7 days, GFAP marker showed a gliotic reaction with alteration of the astrocytes membrane permeability (S100 marker). Positivity for acid phosphatase staining indicated the presence of macrophages. At Day 14 and 21 following MCAO, the histological profile was essentially similar. Interestingly, at Day 7, 14 and 21, a previously unreported gliosis was observed in the subthalamic area. Quantitative analysis showed a significantly large infarct volume at Day 3 (7.88 +/- 1.95 mm3 +/- S.E.M.) compared to Day 7 (4.28 +/- 0.47 mm3 +/- S.E.M.). At Day 14 and Day 21 the infarct volumes were further decreased to 2.00 +/- 0.52 and 1.43 +/- 0.39 mm3 +/- S.E.M., respectively. These results suggest that it is important to consider the time of evaluation of cerebral ischaemia-induced cerebral infarct, especially in studies which aim to evaluate the neuroprotective effect of putative therapeutic agents.
Insights
Middle cerebral artery occlusion (MCAO) in mice causes focal cerebral ischemia. Evaluating infarct volume over time is crucial for assessing neuroprotective agents, as volume significantly decreases between days 3 and 21 post-MCAO.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Ischemic Stroke Models
Background:
- Middle cerebral artery occlusion (MCAO) is a common model for focal cerebral ischemia.
- Understanding the temporal progression of infarcts is essential for stroke research.
Purpose of the Study:
- To characterize the temporal progression of cerebral infarcts following MCAO in mice.
- To quantify infarct volume changes over a 21-day period.
- To highlight the importance of evaluation time in stroke studies.
Main Methods:
- MCAO model in mice.
- Histological staining and immunohistochemical markers (GFAP, S100).
- Qualitative and quantitative analysis of infarct volume at 3, 7, 14, and 21 days post-MCAO.
Main Results:
- MCAO induced focal cerebral ischemia with necrosis, edema, and gliosis.
- Significant infarct volume reduction observed from Day 3 to Day 21.
- Unreported gliosis in the subthalamic area noted at later time points.
Conclusions:
- Infarct volume dynamically changes over time after MCAO.
- The timing of assessment significantly impacts the interpretation of results in stroke research.
- Consideration of temporal dynamics is critical for evaluating neuroprotective therapies.