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.
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.
Stroke. 2022 Oct;53(10):3182-3191. doi: 10.1161/STROKEAHA.122.039641. Epub 2022 Sep 7.
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.
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.
RMP treatment limited hematoma growth following sICH. Hematoma volume (mm) for vehicle- and RMP- (2.66×10 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.
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.
自发性脑出血（sICH）是最致命的中风类型，目前尚无有效的治疗方法。限制血肿扩大是一种有前途的治疗方法。红细胞衍生的微粒（RMPs）是新型止血剂。因此，我们研究了 RMP 在限制血肿生长和改善 sICH 后结果方面的潜力。
通过纹状体内注射胶原酶在大鼠中诱导 sICH。RMP 是用人 RBC 通过高压挤压制备的。sICH 后进行行为和血肿/病变体积评估。确定限制 sICH 后血肿生长所需的 RMP 治疗的最佳剂量、剂量方案和治疗时间窗。我们还评估了 RMP 对 sICH 后长期行为和组织病理学结果的影响。
RMP 治疗可限制 sICH 后的血肿生长。载体和 RMP（2.66×10 个颗粒/kg）治疗组的血肿体积（mm）分别为 143±8 和 86±4。确定了限制血肿扩大的最佳 RMP 给药方案。RMP 在 sICH 后 4.5 小时内给药可限制血肿体积。与对照组相比，4.5 小时后 sICH 的 RMP 治疗组血肿体积降低了 24%。RMP 治疗还改善了 sICH 后的长期组织病理学和行为结果。
我们的结果表明，RMP 治疗可限制血肿生长并改善大鼠模型中 sICH 后的结果。因此，RMP 有可能限制 sICH 患者的血肿生长。
