CD47 blocking antibody accelerates hematoma clearance and alleviates hydrocephalus after experimental intraventricular hemorrhage.
CD47 blocking antibody accelerates hematoma clearance and alleviates hydrocephalus after experimental intraventricular hemorrhage.
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CD47阻断抗体会加速血肿清除，并在实验性脑室出血后减轻脑积水。
DOI：
10.1016/j.nbd.2021.105384
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发表时间：
2021-07
影响因子：
6.1
通讯作者：
Garton HJL
中科院分区：
文献类型：
--
作者：
Ye F;Hua Y;Keep RF;Xi G;Garton HJL
CD 47是红细胞膜上的糖蛋白，通过与吞噬细胞上的信号调节蛋白α相互作用来抑制吞噬作用。我们以前的研究已经证明，阻断CD 47可以加速脑出血后血肿清除并减少脑损伤。本研究探讨了吞噬作用或红细胞CD 47是否影响脑室内出血（IVH）后血肿消退和脑积水的发展。成年（3月龄）雄性Fischer 344大鼠脑室注射200 μl自体血，混合CD 47阻断抗体或同种型IgG，或200 μl生理盐水作为对照。在CD 47阻断抗体处理的大鼠亚组中，共注射氯膦酸盐脂质体（以消耗小胶质细胞/单核细胞衍生的巨噬细胞）或对照脂质体。使用磁共振成像（MRI）评价脑室体积和脑室内T2* 病变体积（估计血肿体积）。在4或72小时后收获脑用于组织学以评价吞噬作用。在成年雄性大鼠中，CD 47阻断抗体缓解了第3天的脑积水发展。此外，CD 47阻断抗体减少了IVH后第1天至第3天的脑室内T2* 病变和T2* 非低信号病变大小。IVH后4小时即可观察到红细胞吞噬作用，并在第3天增强。此外，血肿内浸润的CD 68，血红素加氧酶-1和铁蛋白阳性吞噬细胞上调CD 47封锁的第3天。氯膦酸盐脂质体共注射引起更严重的脑积水和体重减轻。阻断血肿中的CD 47可加速血肿清除，减轻IVH后溶血和脑积水的发展，提示CD 47可能在IVH的未来治疗中有价值。
CD47, a glycoprotein on red blood cell membranes, inhibits phagocytosis via interaction with signal regulatory protein α on phagocytes. Our previous research has demonstrated that blocking CD47 accelerates hematoma clearance and reduces brain injury after intracerebral hemorrhage. The current study investigated whether phagocytosis or erythrocyte CD47 impacts hematoma resolution and hydrocephalus development after intraventricular hemorrhage (IVH). Adult (3-month-old) male Fischer 344 rats were intraventricularly injected with 200 μl autologous blood, mixed with either CD47 blocking antibody or isotype IgG, or 200 μl saline as control. In subgroups of CD47 blocking antibody treated rats, clodronate liposomes (to deplete microglia/monocyte-derived macrophages) or control liposomes were co-injected. Magnetic resonance imaging (MRI) was used to evaluate ventricular volume and intraventricular T2* lesion volume (estimating hematoma volume). The brains were harvested after 4 or 72 hours for histology to evaluate phagocytosis. In adult male rats, CD47 blocking antibody alleviated hydrocephalus development by day 3. In addition, the CD47 blocking antibody reduced intraventricular T2* lesion and T2* non-hypointense lesion size after IVH through day 1 to day 3. Erythrophagocytosis was observed as soon as 4 hours after IVH and was enhanced on day 3. Furthermore, intra-hematoma infiltration of CD68, heme oxygenase-1 and ferritin positive phagocytes were upregulated by CD47 blockade by day 3. Clodronate liposomes co-injection caused more severe hydrocephalus and weight loss. Blocking CD47 in the hematoma accelerated hematoma clearance and alleviated hemolysis and hydrocephalus development after IVH, suggesting CD47 might be valuable in the future treatment for IVH.
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影响因子：
4.1
作者：
Rosen, David S.;Macdonald, R. Loch;Rosengart, Axel J.
通讯作者：
Rosengart, Axel J.
影响因子：
6.3
作者：
Gao, Chao;Du, Hanjian;Xi, Guohua
通讯作者：
Xi, Guohua
影响因子：
6.9
作者：
Dang G;Yang Y;Wu G;Hua Y;Keep RF;Xi G
通讯作者：
Xi G
DOI：
10.1016/s0140-6736(16)32410-2
发表时间：
2017-02-11
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hanley DF;Lane K;McBee N;Ziai W;Tuhrim S;Lees KR;Dawson J;Gandhi D;Ullman N;Mould WA;Mayo SW;Mendelow AD;Gregson B;Butcher K;Vespa P;Wright DW;Kase CS;Carhuapoma JR;Keyl PM;Diener-West M;Muschelli J;Betz JF;Thompson CB;Sugar EA;Yenokyan G;Janis S;John S;Harnof S;Lopez GA;Aldrich EF;Harrigan MR;Ansari S;Jallo J;Caron JL;LeDoux D;Adeoye O;Zuccarello M;Adams HP Jr;Rosenblum M;Thompson RE;Awad IA;CLEAR III Investigators
通讯作者：
CLEAR III Investigators
影响因子：
8
作者：
Adams-Chapman, Ira;Hansen, Nellie I.;Higgins, Rose
通讯作者：
Higgins, Rose