We discuss microglial and macrophage morphologies and phenotypic changes in response to acute brain damage and repair in the context of stroke.

We argue that future translational studies should be targeting multiple key regulating molecules with a concept of “therapeutic time window”.

We suggest that constructing new experimental stroke models should be considered.

We suggest that identifying new gene signatures for circulating immune cells when they enter into the CNS should be considered.

We suggest that exploring the endogenous neuroprotective mechanisms responsible for brain repair should be considered.