A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber
A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber
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DOI：
10.1007/s12975-023-01144-6
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发表时间：
2023-03
影响因子：
6.9
通讯作者：
T. Komatsu;Hiroki Ohta;Naoki Takakura;J. Hata;Tomomichi Kitagawa;Yuta Kurashina;H. Onoe;H. Okano-H.
中科院分区：
文献类型：
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作者：
T. Komatsu;Hiroki Ohta;Naoki Takakura;J. Hata;Tomomichi Kitagawa;Yuta Kurashina;H. Onoe;H. Okano-H.
包括干细胞治疗在内的神经保护治疗相关临床试验的失败，部分原因可能是缺乏合适的动物模型。我们开发了一种干细胞可植入的不透射线水凝胶微纤维，它可以在体内存活很长时间。该超纤维由含有二氧化锆的海藻酸钡水凝胶制成，在双同轴层流微流控装置中制备。我们的目标是利用这种超细纤维开发一种新的焦点中风模型。选取雄性Sprague-Dawley大鼠（n=14），采用数字减影血管造影术将导管（内径0.42 mm，外径0.55 mm）从尾侧腹动脉引导至左侧颈内动脉。通过缓慢注射肝素化生理盐水，将不透射线的水凝胶微纤维（直径0.4 mm，长度1mm）通过导管推进，建立局部闭塞。脑卒中模型建立后3、6 h进行9.4-T磁共振成像，24 h进行2% 2,3,5-三苯四氯化氮染色。测量神经功能缺损评分和体温。所有大鼠均选择性栓塞大脑前动脉-大脑中动脉分叉。手术时间中位数为4 min（四分位数间距[IQR]， 3-8 min）。闭塞后24小时平均梗死体积为388 mm3（IQR, 354-420 mm3）。未见丘脑或下丘脑梗死。体温随时间变化不显著（P= 0.204）。然而，造模前、造模后3、6、24 h的神经功能缺损评分差异有统计学意义（P< 0.001）。我们提出了一种新的大鼠局灶性梗死模型，局限于大脑中动脉区域，使用不透射线的水凝胶微纤维在透视引导下定位。通过在卒中模型中比较含干细胞纤维和不含干细胞纤维的使用，有可能确定“纯”细胞移植治疗卒中的疗效。
AbstractsThe failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3–8 min). Mean infarct volume was 388 mm3(IQR, 354–420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P= 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P< 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke.