From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
Stroke. 2014 Aug;45(8):2431-7. doi: 10.1161/STROKEAHA.113.004460. Epub 2014 Jul 1.
We aimed to determine a possible synergistic effect of granulocyte colony-stimulating factor (G-CSF) and bone marrow-derived mononuclear cells (BM MNC) after stroke in spontaneously hypertensive rats.
Male spontaneously hypertensive rats were subjected to middle cerebral artery occlusion and randomly assigned to daily injection of 50 μg/kg G-CSF for 5 days starting 1 hour after stroke (groups 1, 2, and 3) with additional intravenous transplantation of 1.5×10E7 BM MNC per kilogram at 6 hours (group 2) or 48 hours (group 3) after stroke, or control treatment (group 4). Circulating leukocyte counts and functional deficits, infarct volume, and brain edema were repeatedly assessed in the first week and first month.
G-CSF treatment led to a significant neutrophilia, to a reversal of postischemic depression of circulating leukocytes, and to a significantly improved functional recovery without affecting the infarct volume or brain edema. BM MNC cotransplantation was neutral after 6 hours, but reversed the functional effect of G-CSF after 48 hours. Short-term investigation of combined G-CSF and BM MNC treatment at 48 hours indicated splenic accumulation of granulocytes and transplanted cells, accompanied by a significant rise of granulocytes in the circulation and the ischemic brain.
G-CSF improved functional recovery in spontaneously hypertensive rats, but this effect was abolished by cotransplantation of BM MNC after 48 hours. In the spleen, transplanted cells may hinder the clearance of granulocytes that were massively increased by G-CSF. Increased circulation and infiltration of granulocytes into the ischemic brain may be detrimental for stroke outcome.
我们旨在确定粒细胞集落刺激因子（G-CSF）和骨髓来源的单核细胞（BM MNC）在自发性高血压大鼠中风后的协同作用。
雄性自发性高血压大鼠接受大脑中动脉闭塞，并随机分为中风后 1 小时开始每天注射 50μg/kg G-CSF 5 天的组（1、2 和 3 组），并在中风后 6 小时（2 组）或 48 小时（3 组）额外静脉内移植每公斤 1.5×10E7 BM MNC，或接受对照治疗（4 组）。在第一周和第一个月内，反复评估循环白细胞计数和功能缺陷、梗死体积和脑水肿。
G-CSF 治疗导致显著的中性粒细胞增多，逆转了缺血后循环白细胞的抑制，并显著改善了功能恢复，而不影响梗死体积或脑水肿。BM MNC 共移植在 6 小时后呈中性，但在 48 小时后逆转了 G-CSF 的功能作用。对 48 小时联合 G-CSF 和 BM MNC 治疗的短期研究表明，粒细胞和移植细胞在脾脏蓄积，同时循环和缺血性脑内的粒细胞显著增加。
G-CSF 改善了自发性高血压大鼠的功能恢复，但在 48 小时后共移植 BM MNC 会消除这种作用。在脾脏中，移植细胞可能会阻碍因 G-CSF 而大量增加的粒细胞的清除。循环中粒细胞的增加和浸润到缺血性脑内可能对中风结果有害。
