A novel combined model of intracerebral and intraventricular hemorrhage using autologous blood-injection in rats

Abstract

Intracerebral hemorrhage (ICH) is the least treatable form of stroke and is associated with the worst prognosis. In up to 40% of cases, ICH is further complicated by intraventricular hemorrhage (IVH), which predisposes to hydrocephalus, and increases case-mortality to 80%. However, IVH is not present in widely used preclinical models of ICH. Here, we characterize a novel rat model of combined ICH and IVH. Rats were injected with different volumes of autologous whole blood into the right deep basal ganglia region (100μL, 150μL, 200μL, and 250μL, n=10 per group). MRI was performed immediately, and at 24, 48, 72h, and 1week after blood injection, along with neurological evaluations. Injected blood volume reliably correlated with blood volumes measured from MRI obtained after blood injection. Brain edema was most prominent in the ⩾200μL groups, peaking at 48h in all groups, being statistically different between the ⩾200μL and <200μL groups at all-time points. Presence of hydrocephalus was detected in most of the animals, most clearly in the 200μL and 250μL groups, both being statistically different from the 100μL group at all-time points, with tendency to worsen during the whole follow-up period. Most deteriorating neurological and behavioral outcomes as well as the highest mortality rates were detected in groups injected with 200μL and 250μL of autologous blood, 40% and 70%, respectively. These volumes were most similar to the clinical scenario of combined ICH and IVH, demonstrating that this novel rat model is a promising starting point for future ICH+IVH research.