Abstract Body: Background: Spontaneous intracerebral hemorrhage (sICH) is a neurological condition characterized by the rupture of blood vessels within the brain, resulting in the formation of a hematoma and subsequent brain injury. Tobacco use is a major modifiable risk factor for sICH and is associated with worsened outcomes following the occurrence of sICH. Tobacco use is also correlated with worsened outcomes following sICH. Previously, we observed that prior chronic exposure to nicotine results in increased hematoma volume following collagenase-induced sICH when compared to saline-exposed animals. This study aims to evaluate the effect of prior chronic nicotine exposure on long-term outcomes post-sICH.

Hypothesis: Prior chronic nicotine exposure will result in more significant brain damage following an autologous blood injection-induced sICH.

Methods: Young male and female (estrous matched) rats were randomly assigned to a saline (control) or nicotine-exposed group. Rats received nicotine or saline via. osmotic pumps for 2-3 weeks. The pump was removed before the induction of sICH by the stereotaxic injection of autologous blood into the striatum. The autologous blood injection-induced sICH model was used to obtain equal hematoma volume in all experimental groups. Rats then underwent perfusion fixation, and brains were harvested for histopathological analysis. Paraffin-embedded brain blocks were cut into 10 µm coronal sections between bregma -2.0 to +2.0, stained with hematoxylin and eosin, scanned with a high-resolution scanner, and analyzed using ImageJ to measure lesion area. Student’s t-test was used to determine significant differences in mean lesion volume between treatment groups. Two-way ANOVA was used to assess the interaction effect between sex and lesion volume.

Results: For the male group, the brain lesion volume in nicotine-exposed rats was significantly (p<0.01) larger by 121% (6.11± 0.81 mm³) when compared to the lesion volume in saline-exposed rats (2.77± 0.26 mm³). For the female group, the brain lesion volume of the nicotine group was significantly (p<0.01) larger by 62% (4.98±0.39 mm³) when compared to the lesion volume of the saline group (3.07± 0.53 mm³). Sex had no significant effect on mean lesion volume.

Conclusion: Chronic nicotine exposure worsens long-term outcomes post-sICH in young rats of both sexes.