Neuropathological changes in the brain of pigs with acute liver failure
Neuropathological changes in the brain of pigs with acute liver failure
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DOI：
10.3109/00365521003675047
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发表时间：
2010-08-01
影响因子：
1.9
通讯作者：
Rose, Christopher F.
中科院分区：
文献类型：
--
作者：
Kristiansen, Rune Gangsoy;Lindal, Sigurd;Rose, Christopher F.
objective.脑水肿是急性肝功能衰竭（ALF）的严重并发症，可导致颅内高压和死亡。公认的原则是血脑屏障是完整的，脑水肿主要是由高氨血症引起的细胞毒性病因引起的。然而，对ALF的神经病理学改变研究甚少。使用一个良好的猪模型，我们的目的是研究超微结构的变化，从猪患有ALF。材料和方法。将16头体重为27 - 35 kg的雌性挪威长白猪随机分为两组：ALF组（n = 8）和假手术对照组（n = 8）。ALF诱导与端侧门腔静脉分流，然后结扎肝动脉。ALF 8小时后，从大脑的三个不同区域（额叶、小脑和脑干）采集活检组织，并使用电子显微镜进行分析。结果在所有三个区域均发现了严重的血管周围和间质水肿。观察到周细胞和星形胶质细胞过程的破坏，反映了患有ALF的动物中血脑屏障的破坏/病变。此外，神经元和轴突水肿，并被囊泡包围。在小脑和脑干中分别观察到浦肯野神经元严重损伤（坏死）和髓鞘受损。来自假手术动物的活检是正常的。结论.我们的数据支持血管源性脑水肿在ALF猪颅内高压的发展中起重要作用的观点。
Objective. Cerebral edema is a serious complication of acute liver failure (ALF), which may lead to intracranial hypertension and death. An accepted tenet has been that the blood-brain barrier is intact and that brain edema is primarily caused by a cytotoxic etiology due to hyperammonemia. However, the neuropathological changes in ALF have been poorly studied. Using a well characterized porcine model we aimed to investigate ultrastructural changes in the brain from pigs suffering from ALF. Materials and methods. Sixteen female Norwegian Landrace pigs weighing 27-35 kg were randomised into two groups: ALF (n = 8) and sham operated controls (n = 8). ALF was induced with an end-to-side portacaval shunt followed by ligation of the hepatic arteries. Biopsies were harvested from three different areas of the brain (frontal lobe, cerebellum, and brain stem) following eight hours of ALF and analyzed using electron microscopy. Results. Profound perivascular and interstitial edema were found in all three areas. Disruption of pericytic and astrocytic processes were seen, reflecting breakdown/lesion of the blood-brain barrier in animals suffering from ALF. Furthermore, neurons and axons were edematous and surrounded by vesicles. Severe damage to Purkinje neuron (necrosis) and damaged myelin were seen in the cerebellum and brain stem, respectively. Biopsies from sham operated animals were normal. Conclusions. Our data support the concept that vasogenic brain edema plays an important role in the development of intracranial hypertension in pigs with ALF.