Abstract TP126: The Therapeutic Window Of Red Cell Microparticles In Limiting Intracerebral Hemorrhage-induced Hematoma Growth In Nicotine-exposed Rats.

Abstract

Spontaneous intracerebral hemorrhage (sICH) is a subtype of hemorrhagic stroke with enormous mortality and morbidity, and tobacco use is one of the major risk factors for sICH. We have shown that red cell microparticle (RMP) treatment limits hematoma growth following sICH in nicotine-exposed rats. Presently, we determined the therapeutic time window of RMP efficacy. RMPs were generated from RBCs using high pressure extrusion. Rats were treated for a period of 2-3 weeks with nicotine (4.5 mg / kg b.w./ day, s.c.) using osmotic pumps. sICH was induced using intra-striatal collagenase administration. Rats of either sex were randomized between saline (vehicle) or RMP treatment groups (n=10 each for 4.5 h and 6 h RMP treatment time points, n=15 each for pooled vehicle time points). Males treated at 4.5 h and females treated at both timepoints received ~1.34х10 11 particles/ kg b.w., i.v. over 2 h period. While males treated at 6 h received ~ 1.58х10 11 particles/ kg b.w., i.v. over 2 h duration. After ~24 hours, functional deficit was assessed using neurological scores, and hematoma volume was measured in a blinded manner. The hematoma volume of male rats treated with RMPs 4.5 h post-sICH (94±3 mm 3 ) was significantly lower (p<0.05) than the controls (119±7 mm 3 ). Moreover, the neurological score of male rats treated with RMPs 4.5 h post-sICH (8.9±0.5) was significantly lower (p<0.005) than the controls (10.9±0.2). However, the hematoma volume (103±12 mm 3 ) and neurological score (10.1±0.6) of the 6 h post-sICH RMP treatment male group were not different from the controls. The hematoma volume observed in female rats treated with RMPs 4.5 h post-sICH (60±6 mm 3 ) was significantly lower (p<0.01) than the controls (99±2 mm 3 ). Further, neurological score of the rats treated with RMPs 4.5 h post-sICH (7.7±0.6) was significantly lower (p<0.001) than the controls (10.1±0.2). However, the hematoma volume (96±8 mm 3 ) and neurological score (10.4±0.3) in female rats treated with RMPs 6 h post-sICH were not different from the controls. Our results show that RMPs limit hematoma growth in nicotine-exposed rats when administrated 4.5 h post-sICH induction. Thus, RMPs may lower hematoma growth in sICH patients following tobacco use. Support: James Esther King Biomedical Research Grant 9JK08.