105 Creation and Optimization of a Translational Rodent Model of Cerebrovascular Disease

INTRODUCTION: Spontaneous intracerebral hemorrhage (ICH) continues to have devastating morbidity and mortality, with little progress in managing resultant secondary injury. We have created a cardiometabolic model of ICH using transgenic (mRen2)27 rats to mirror the comorbidities of patients with ICH. METHODS: Body weight, blood pressures (BP), sensorimotor testing, cerebrovascular histology, and pro-inflammatory cytokines were quantified in (mRen2)27 and compared with control Hanover Sprague Dawley (SD) in both sexes (n = 32). A stereotaxically-assisted single-injection autologous-blood ICH in the basal ganglia was performed and hemoglobin quantified at 24/72 hours to assess reabsorption (n = 28). RESULTS: Mean blood pressures and weights were higher in the cardiometabolic (mRen2)27 strain at baseline (p < 0.005). There were no between-strain differences in sensorimotor testing up to 28 weeks. At 30 weeks, (mRen2)27s had higher serum IL-12 than SDs in both males (p < 0.05) and females (p < 0.05). (mRen2)27 females had higher IL-12 than males (p < 0.05). At 32-weeks, (mRen2)27 males (p < 0.0001) had increased wall to lumen ratios (W:L), signifying hyalinization. At 52-weeks, there was an increase in W:L ratio in both male (p < 0.01) and female (p < 0.05) (mRen2)27s compared to control. There was a difference in amount of residual hemoglobin between male SD and (mRen2)27’ ipsilateral hemispheres 72 hours post-ICH (p < 0.05), demonstrating impaired ICH resolution. CONCLUSIONS: There is a need for effective pre-clinical models of ICH. We characterized a cardiometabolic model of ICH that possesses parody at baseline with the traditional rodent model and demonstrates significant strain and sex differences after ICH. (mRen2)27s had delayed hematoma resolution, decrease-in-function morphological changes, and pro-inflammatory cytokine upregulation. These differences provide insight into the mechanism of cerebrovascular injury and may act as targets for translational therapeutics.