Habitual exercise prior to intracerebral hemorrhage primes brain environment against injury in a dose-dependent manner of the exercise.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with limited treatment options. Although exercise is beneficial in ischemic stroke, its preconditioning effects in hemorrhagic stroke remain unclear. We examined whether voluntary wheel running prior to ICH modulates acute outcomes and gene expression. Male ICR mice underwent three weeks of voluntary running or sedentary housing before ICH induction. Neurological function was assessed 3 days post-ICH, and perihematomal tissue was analyzed by quantitative PCR. ICH increased expression of Iba1, GFAP, C3, MMP9, TIMP1, and Caspase3, while reducing BDNF expression. Exercise preconditioning did not improve acute behavioral deficits at the group level. However, running distance strongly predicted molecular and pathological responses. BDNF expression correlated positively with exercise volume, whereas C3 showed a negative correlation, with a similar trend for GFAP. Caspase3 and Bax expression were negatively correlated with running distance. Although hematoma volume did not differ significantly between groups, greater running distance was associated with smaller hematoma volume within the exercise group. These findings indicate that habitual voluntary exercise does not attenuate acute functional deficits after ICH but induces dose-dependent molecular adaptations related to neuroplasticity, glial inflammation, and cell death, potentially priming the brain for enhanced recovery in later phases.