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在具有晚期自发再灌注的成年小鼠中建立光血栓形成“环”卒中模型:脑血流量和脑蛋白质合成的定量测量

Establishing a photothrombotic 'ring' stroke model in adult mice with late spontaneous reperfusion: quantitative measurements of cerebral blood flow and cerebral protein synthesis.

作者信息

Jiang Wei, Gu Weigang, Hossmann Konstantin-Alexander, Mies Günter, Wester Per

机构信息

Umeå Stroke Center, University of Umeå, Umeå, Sweden.

出版信息

J Cereb Blood Flow Metab. 2006 Jul;26(7):927-36. doi: 10.1038/sj.jcbfm.9600245. Epub 2005 Nov 16.

Abstract

This study sought to establish the photothrombotic 'ring' stroke model with late spontaneous reperfusion in adult mice. By applying a 3.0-mm diameter laser ring-beam (514 nm, 0.21 mm thick, 0.65 W/cm2) onto the exposed skull for 60 secs with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15 secs, the centrally located cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit. In this region, local cerebral blood flow (lCBF) measured by laser-Doppler flowmetry declined promptly after irradiation to 43% of the baseline value at 30 mins poststroke. Using double tracer autoradiography, quantitative lCBF measured with [14C]iodoantipyrine was 46 to 17 to 58 ml/100 g/mins at 4 h to 48 h to 7 days postischemia in this area. Cerebral protein synthesis (CPS), as detected by [3H]leucine incorporation into protein, transiently decreased to 57% to 38% to 112% at 4 h to 48 h to 7 days postischemia in the center region. Morphologically, some neurons in the center region appeared swollen at 4 h. At 48 h, the majority of neurons were severely swollen with eosinophilia and pyknosis, whereas at 7 days poststroke' the tissue morphology became partly restored. The center within the mouse photothrombotic ring lesion thus exhibits reversible alterations of local CBF, CPS and tissue morphology that are reminiscent of the cortical penumbra in other models of focal cerebral ischemia.

摘要

本研究旨在建立成年小鼠具有晚期自发再灌注的光血栓性“环形”卒中模型。通过将直径3.0毫米的激光环形光束(514纳米,0.21毫米厚,0.65瓦/平方厘米)照射到暴露的颅骨上60秒,同时静脉输注赤藓红B(4.25毫克/千克)15秒,环形区域内位于中心的皮质区域逐渐被环形灌注缺损所侵犯。在该区域,通过激光多普勒血流仪测量的局部脑血流量(lCBF)在照射后迅速下降,在卒中后30分钟降至基线值的43%。使用双示踪剂放射自显影术,在缺血后4小时至48小时至7天,用[14C]碘安替比林测量的该区域定量lCBF为46至17至58毫升/100克/分钟。脑蛋白合成(CPS),通过[3H]亮氨酸掺入蛋白检测,在缺血后4小时至48小时至7天,中心区域短暂下降至57%至38%至112%。形态学上,中心区域的一些神经元在4小时时出现肿胀。在48小时时,大多数神经元严重肿胀,伴有嗜酸性粒细胞增多和核固缩,而在卒中后7天,组织形态部分恢复。因此,小鼠光血栓性环形病变内的中心区域表现出局部CBF、CPS和组织形态的可逆性改变,这让人联想到其他局灶性脑缺血模型中的皮质半暗带。

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