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Background The effects of performing a minimally invasive procedure at different stages after intracerebral hemorrhage on perihematomal MMP-9 expression and blood-brain barrier (BBB) permeability were evaluated. Methods Sixty rabbits were randomly distributed into a model control group (MC group, 30 rabbits) or a minimally invasive group (MI group, 30 rabbits). A model of intracerebral hemorrhage was established in the MC and MI group. In the MI group, the intracerebral hematoma was evacuated by stereotactic minimally invasive procedures over 6 hours (6 rabbits), 12 hours (6 rabbits), 18 hours (6 rabbits) 24 hours or 48 hours (6 rabbits) following successful induction of intracerebral hemorrhage. The same procedure was performed in the MC group at the same time point but without evacuating the hematoma. All the animals were sacrificed within two weeks after the hematoma was surgically evacuated. A neurological deficit score was determined, and the perihematomal MMP-9 level and the BBB permeability were measured. Results The neurological deficit score, perihematomal MMP-9 level and BBB permeability of the MI group decreased significantly compared to the MC group. Performing the MI procedure 6-12 h after intracerebral hemorrhage showed the most favorable outcome. Conclusions Regarding the pathophysiological changes surrounding the hematoma, the optimal time window of performing MI procedures for the intracerebral hematoma evacuation might be within 6-12 h after hemorrhage. [ABSTRACT FROM AUTHOR]