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

以大鼠局灶性脑缺血为对照，观察脂肪栓塞组大鼠脑水肿形成过程中的星形胶质细胞反应和水通道蛋白4(AQP-4)的变化。脑含水量在颈动脉注射三油酸后2~72h升高，但三个评价时间点之间无差异。组织学检查可见核内细节消失，尼氏小体和核固缩。胞浆内可见空泡变性，神经元及小血管周围可见光晕形成。注射后2~72h，周围病变星形胶质细胞反应性增强，72h时星形胶质细胞反应性增强，并伴有肥大和有丝分裂。注射PEN后2~72h，皮损中心AQP4表达明显增强，但皮损中心未见AQP4表达。MCAO后2小时，仅见核固缩，尼氏小体消失。虽然病变周围可见星形胶质细胞反应，但脑水含量无明显增加，AQP4免疫染色无明显变化。与MCAO组相比，TRAO组大鼠脑内基底膜免疫染色呈下降趋势。本研究结果表明，与MCAO组相比，脂肪栓塞组在脑损伤后早期即出现AQP4和基底膜的严重脑水肿，而脑含水量和AQP4变化不明显。而星形胶质细胞的反应性在注射后72h开始增强，并伴有肥大和有丝分裂，与MCAO的报道一致。需要早期治疗，以防止脂肪栓塞患者的脑损伤和水肿形成，而AQP4通道和基质金属蛋白酶的调节将引领新的治疗策略。

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.