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

我们观察了脂肪栓塞模型大鼠脑水肿形成过程中的星形细胞反应和水通道蛋白（AQP）4谱，并与局灶性脑缺血模型进行了比较。颈动脉内注射三油苷后2 ~ 72 h脑含水量升高，3个评价时间点间无差异。组织学检查显示细胞核细节消失，尼氏小体和细胞核固缩。细胞质空泡变性，神经元和小血管周围形成晕。注射后2 ~ 72h，病变周围星形胶质细胞反应性增强，注射后72h星形胶质细胞增生、有丝分裂。注射后2 ~ 72 h， AQP4免疫染色在笔感染的病变中明显升高，但在病变核心处不可见。MCAO 2小时后，仅见核固缩，尼氏体消失。虽然病变周围可见星形胶质细胞反应性，但脑含水量未见明显升高，AQP4免疫染色未见明显改变。与MCAO组相比，三油苷组的基底膜免疫染色倾向较低。本研究表明，三油酸脂栓塞在损伤后早期会产生严重的脑水肿，伴有AQP4和基板调节，与MCAO相比，2 h后含水量和AQP4没有明显增加。但星形胶质细胞反应性增强，注射三油苷后72h呈肥大和有丝分裂，与MCAO先前报道一致。在脂肪栓塞病例中，需要早期治疗来预防脑损伤和水肿形成，AQP4通道和基质金属蛋白酶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.