EXPRESS: Brain on fire: Why intracerebral hemorrhage requires a firefighting strategy beyond single therapeutic targets

Intracerebral hemorrhage (ICH) remains the most lethal form of stroke and lacks an established neuroprotective therapy. Secondary injury after ICH reflects interacting processes, including hematoma expansion, hemolysis-derived toxicity, neuroinflammation, blood-brain barrier dysfunction, perihematomal edema, oxidative stress, and regulated cell death. Although mechanistic single-target studies remain essential for defining biological relevance, treatment windows, target engagement, and safety, ICH is unlikely to be adequately addressed by any one intervention alone. Using the analogy of a “fire in the brain,” this perspective proposes a coordinated, time-sensitive firefighting framework: Rapid blood-pressure management and hemostatic reversal can limit continued bleeding. Hematoma evacuation can remove biological fuel in selected patients. Interventions targeting lipid peroxidation and oxidative injury may limit secondary combustion. Inflammation- and edema-directed therapies may contain harmful heat. Enhancement of endogenous hematoma clearance may promote resolution and repair. Imaging and biomarkers can support phenotyping, monitoring, and treatment selection. Emerging signals from care bundle, minimally invasive evacuation, and experimental combination studies support the testing of staged, biologically rational add-on strategies rather than fixed therapeutic cocktails. The goal is not to deploy all the tools at once, but to match appropriate interventions to the evolving biology, phenotype, timing, feasibility, and care context of each hemorrhage.