Spatiotemporal Remodeling of Neural Excitability Following Ischemic Stroke: Regional Mechanisms From the Infarct Core to Brainstem–Spinal Output Systems: A Structured Narrative Review

Changes in neural excitability after ischemic stroke affect lesion growth, recovery of function, and long‐term motor problems. People often think of these changes as just an increase or decrease in neural activity. This view does not explain why excitability changes are different at different stages, brain regions, or mechanisms. It also does not explain why these changes can cause injury, help recovery, or lead to maladaptation. In the acute phase, the main areas involved are the infarct core and the ischemic penumbra. Here, excitability problems include membrane instability, prolonged depolarization, spreading depolarizations (SDs), changes in the fluid environment, and abnormal neurovascular responses. These problems together create harmful excitability that makes the lesion bigger. In the subacute phase, the dominant substrates shift toward the peri‐infarct cortex, ipsilesional primary motor cortex, and bilateral sensorimotor networks. Here, excitability changes are defined by excitatory–inhibitory rebalancing, reduction of excessive tonic inhibition, restoration of cortical responsiveness, and experience‐dependent network reorganization, forming restorative excitability that supports neural plasticity and functional recovery. During the subacute phase, excitatory–inhibitory rebalancing becomes a key synaptic mechanism of recovery, involving glutamatergic transmission, γ‐aminobutyric acid (GABA)ergic tonic and phasic inhibition, synaptic scaling, dendritic remodeling, and activity‐dependent refinement of surviving peri‐infarct circuits. In the chronic phase, in a subset of patients, the dominant substrates further shift toward the brainstem‐spinal output system, where compensatory recruitment of alternative descending pathways may contribute to abnormal synergies, spasticity, and low‐resolution motor control, representing maladaptive hyperexcitability. We therefore argue that poststroke excitability should not be interpreted within a static high‐/low‐excitability dichotomy but defined by when it occurs, where it is expressed, and at which mechanistic level it predominates.