Long-term validity of the microglial dynamics ODE model

Determine whether the proposed coupled ordinary differential equation model for M1 and M2 microglial cell counts in the mouse penumbra following middle cerebral artery occlusion—using logistic time-dependent activation functions and constant phenotype-switching and mortality rates—accurately captures biologically relevant microglial dynamics over time horizons longer than the two-week observation period.

Background

The paper develops a two-equation ODE model for M1 and M2 microglial cells in the penumbra after MCAO, with logistic activation functions and constant switching and mortality rates. Forecasts beyond the observed two-week data suggest a persistent elevated level of M1 cells and near steady-state behavior, whereas biological expectations include a possible return to baseline cell counts around or after Day 35.

This discrepancy motivates a validation question about the model’s ability to represent longer-term dynamics and indicates that additional experimental observations may be required and that modifications (e.g., to the M1 activation function) might be necessary if the current formulation fails to capture long-term behavior.