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Form of the lingering inflammatory response between Days 14–35 is unknown

Characterize the form of the lingering neuroinflammatory response in the penumbra between Day 14 and Day 35 after middle cerebral artery occlusion-induced ischemic stroke in mice, determining whether microglial cell counts reach a steady state, exhibit oscillations, or change slowly over time.

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Background

To assess and validate forecast predictions beyond the 14-day data window, the authors adopt evaluation criteria from related experimental studies. They explicitly note that while inflammation may linger between Days 14 and 35, its form is unknown.

This uncertainty encompasses multiple plausible behaviors (steady state, oscillatory dynamics, or slow monotonic change), and resolving it is essential for accurate long-term prediction and biological interpretation of microglial activity post-stroke.

References

In particular, we use the following three criteria: (i) the amount of M1 cells may still be significantly greater than the amount of M2 cells from Day 14 on; (ii) between Day 14 and Day 35 there may be some lingering inflammatory response; however, the form of this response is unknown (i.e., the number of cells may have reached a steady state, may be oscillating, or may be increasing/decreasing slowly); and (iii) after Day 35, we may assume that the amount of M1 and M2 cells decreases towards their respective baseline value.

Data-driven modeling and prediction of microglial cell dynamics in the ischemic penumbra (2404.10915 - Amato et al., 16 Apr 2024) in Section 3, Results