Time-Dependent Neuroprotection and Precision Interventions in Acute Ischemic Stroke in the Reperfusion Era

Acute ischemic stroke ranks as the second leading cause of mortality among noncommunicable diseases globally. Although recent advancements in intravenous thrombolysis and endovascular thrombectomy have markedly increased recanalization rates in patients with large vessel occlusion, improvements in clinical outcomes have not been consistently observed. Accumulating evidence demonstrates that successful recanalization does not necessarily translate into effective tissue reperfusion. Accordingly, the concept of neuroprotection has evolved from a traditional focus on mitigating cellular necrosis toward a strategy aimed at delaying the progression of ischemic penumbra and preserving salvageable brain tissue. This review summarizes the dynamic processes underlying reperfusion injury, microcirculatory dysfunction, neurovascular unit disruption, and associated neuroprotective mechanisms. Particular emphasis is placed on reversible changes within penumbra, reperfusion-induced injury amplification, and emerging imaging-guided approaches and molecular biomarkers for precision interventions. These insights provide a framework for developing spatiotemporally coordinated, individualized neuroprotective strategies.