Ashish K Rehni1,2, Sunjoo Cho1,2, Hever Navarro Quero3, Vibha Shukla1,2, Zhexuan Zhang4, Chuanhui Dong2, Weizhao Zhao4, Miguel A Perez-Pinzon1,2,5, Sebastian Koch2, Wenche Jy3, Kunjan R Dave1,2,5. 1. Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., V.S., M.A.P.-P., K.R.D.), University of Miami Miller School of Medicine, FL. 2. Department of Neurology (A.K.R., S.C., V.S, C.D., M.A.P.-P., S.K., K.R.D.), University of Miami Miller School of Medicine, FL. 3. The Wallace H Coulter Platelet Laboratory, Division of Hematology/Oncology, Department of Medicine (H.N.Q., W.J.), University of Miami Miller School of Medicine, FL. 4. Department of Biomedical Engineering, University of Miami, Coral Gables, FL (Z.Z., W.Z.). 5. Neuroscience Program (M.A.P.-P., K.R.D.), University of Miami Miller School of Medicine, FL.
Abstract
BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is the deadliest stroke subtype with no effective therapies. Limiting hematoma expansion is a promising therapeutic approach. Red blood cell-derived microparticles (RMPs) are novel hemostatic agents. Therefore, we studied the potential of RMPs in limiting hematoma growth and improving outcomes post-sICH. METHODS: sICH was induced in rats by intrastriatal injection of collagenase. RMPs were prepared from human RBCs by high-pressure extrusion. Behavioral and hematoma/lesion volume assessment were done post-sICH. The optimal dose, dosing regimen, and therapeutic time window of RMP therapy required to limit hematoma growth post-sICH were determined. We also evaluated the effect of RMPs on long-term behavioral and histopathologic outcomes post-sICH. RESULTS: RMP treatment limited hematoma growth following sICH. Hematoma volume (mm3) for vehicle- and RMP- (2.66×1010 particles/kg) treated group was 143±8 and 86±4, respectively. The optimal RMP dosing regimen that limits hematoma expansion was identified. RMPs limit hematoma volume when administered up to 4.5-hour post-sICH. Hematoma volume in the 4.5-hour post-sICH RMP treatment group was lower by 24% when compared with the control group. RMP treatment also improved long-term histopathologic and behavioral outcomes post-sICH. CONCLUSIONS: Our results demonstrate that RMP therapy limits hematoma growth and improves outcomes post-sICH in a rodent model. Therefore, RMPs have the potential to limit hematoma growth in sICH patients.
BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is the deadliest stroke subtype with no effective therapies. Limiting hematoma expansion is a promising therapeutic approach. Red blood cell-derived microparticles (RMPs) are novel hemostatic agents. Therefore, we studied the potential of RMPs in limiting hematoma growth and improving outcomes post-sICH. METHODS: sICH was induced in rats by intrastriatal injection of collagenase. RMPs were prepared from human RBCs by high-pressure extrusion. Behavioral and hematoma/lesion volume assessment were done post-sICH. The optimal dose, dosing regimen, and therapeutic time window of RMP therapy required to limit hematoma growth post-sICH were determined. We also evaluated the effect of RMPs on long-term behavioral and histopathologic outcomes post-sICH. RESULTS: RMP treatment limited hematoma growth following sICH. Hematoma volume (mm3) for vehicle- and RMP- (2.66×1010 particles/kg) treated group was 143±8 and 86±4, respectively. The optimal RMP dosing regimen that limits hematoma expansion was identified. RMPs limit hematoma volume when administered up to 4.5-hour post-sICH. Hematoma volume in the 4.5-hour post-sICH RMP treatment group was lower by 24% when compared with the control group. RMP treatment also improved long-term histopathologic and behavioral outcomes post-sICH. CONCLUSIONS: Our results demonstrate that RMP therapy limits hematoma growth and improves outcomes post-sICH in a rodent model. Therefore, RMPs have the potential to limit hematoma growth in sICH patients.
Authors: Marc Fisher; Giora Feuerstein; David W Howells; Patricia D Hurn; Thomas A Kent; Sean I Savitz; Eng H Lo Journal: Stroke Date: 2009-02-26 Impact factor: 7.914