Abstract WP407: Therapeutic Window of Red Cell Microparticles in Limiting Hematoma Growth in a Rat Model of Intracerebral Hemorrhage

Abstract

Spontaneous intracerebral hemorrhage (sICH) is a serious form of stroke without any effective therapy. Limiting hematoma growth is a promising therapeutic strategy. Published data showed that red blood cell-derived microparticles (RMPs) enhance both primary and secondary hemostasis. Previously, we observed that RMPs lower hematoma growth in a rat model of sICH. The goal of our present study was to determine the optimal therapeutic time window for RMP administration. Optimal therapeutic dose and treatment paradigm were used based on our previous studies. RMPs were prepared from human RBCs using high-pressure extrusion. sICH was induced in young male rats by injecting collagenase into the right striatum. Rats were treated with either saline (vehicle) or RMP (2.55х10 10 particles/kg, b.w. i.v.) starting at 2, 3, 4.5, or 6 h post-sICH induction. Rats were randomly assigned to each treatment group (n=10 for each RMP treatment time window, n=5 for each vehicle time window). Neurological scores (12 indicates maximum impairment) were evaluated ~24 h post-collagenase injection, and then, the rats were perfused using saline. Brains were collected and sectioned for hematoma volume assessment using ImageJ by a blinded investigator. The hematoma volumes (mm 3 ) of 2 (53±4, p<0.01), 3 (51±6, p<0.005), and 4.5 h (55±5, p<0.05) post-sICH RMP treatment groups were significantly lower than the vehicle group (72±4, pooled for all time windows). Similarly, the neurological scores in the 2 (8.8±0.5, p<0.001), 3 (9.0±0.3, p<0.001), and 4.5 h (8.8±0.4, p<0.001) post-sICH RMP treatment groups were significantly lower than the vehicle group (10.9±0.2). However, the hematoma volume (65±5) and neurological score (10.2±0.4) in the 6 h post-sICH RMP treatment group were not significantly different from the vehicle group. Our results indicate that RMPs were effective in lowering post-ICH hematoma volume when administrated up to 4.5 h after ICH induction. Together with our earlier results with optimal dose treatment paradigm and long-term outcome studies, these results further support the use of RMPs as a potential therapeutic option to lower hematoma growth in sICH patients.