Astrocytic response, profiles of aquaporin 4 and matrix metalloproteinase contribution to the process of brain edema formation in the fat embolism and focal brain ischemia model in rat

在大鼠脂肪栓塞模型中观察了脑水肿形成过程中星形胶质细胞的反应和水通道蛋白（AQP）4的表达，并与局灶性脑缺血模型进行了比较，结果表明，颈动脉内注射三油酸甘油酯后2~72 h脑含水量增加，三个时间点之间无差异。组织学检查显示细胞核细节消失，尼氏体消失，核固缩。细胞质内可见胞浆内嗜铬细胞变性，神经元和小血管周围有晕圈形成。注射后2~72 h，病变周围星形胶质细胞反应性增强，72 h时肥大、有丝分裂增强。注射后2~72 h，注射笔影响的病变中AQP4免疫染色显着增加，但在病变的核心中不存在。MCAO后2h，仅见细胞核固缩，尼氏体消失。虽然星形胶质细胞反应被认为是在周围受影响的病变，有没有显着增加脑含水量或AQP4免疫染色的变化。结果表明，三油酸甘油酯脂肪栓塞后，脑组织水肿加重，AQP4和基底膜改变较MCAO组早，而MCAO后2h脑组织含水量和AQP4变化不明显，但72h星形胶质细胞反应性增强，肥大，有丝分裂根据先前的MCAO报告，在三油酸甘油酯注射后。脂肪栓塞患者需要早期治疗以防止脑损伤和水肿形成，AQP4通道和基质金属蛋白酶调节将成为新的治疗策略。

We examined the astrocytic response and aquaporin (AQP)4 profiles in the process of brain edema formation in the fat embolism model in rat, comparing to those in focal brain ischemia.Brain water content increased 2 to 72 h after intracarotid injection of triolein with no difference among the three evaluation time points. Histological evaluation exhibited the disappearance of the details of nucleus, and Nissl bodies and pyknosis of nuclei. Vacuole degeneration in cytoplasm and halo formation around neurons and small vessels was observed. Reactivity of astrocyte was also increased in peri-affected lesion 2 to 72 h after injection and was strong with hypertrophy and mitosis in the 72h after triolein injection. AQP4 immunostaining was markedly increased in pen-affected lesion but was absent in the core of the lesion 2 to 72 h after injection. Two hour after MCAO, only pyknosis of nuclei, and Nissl bodies disappearance were observed. Although astrocyte reactivity was seen in the peri-affected lesion, there was no significant increase of brain water content or changes in AQP4 immunostaining. Immunostaining of basal lamina is tended to be lower in the triolein groups than the MCAO group.The present study showed that fat embolism with triolein produces severe brain edema with AQP4 and basal lamina modulation at early stage after the insult in a quite contrast with MCAO after 2 h without significant increase in water content and AQP4 changes.However astrocytes reactivity became strong with hypertrophy and mitosis in the 72h after triolein injection with accordance with the previous MCAO report. Early therapy would be needed to prevent brain damage as well as edema formation in fat embolism cases and AQP4 channel and matrix metalloproteinase modulation would lead the new therapeutic strategy.