Endogenous toxicity caused by systemic inflammation as well as by acute liver failure triggers a wide range of dysfunctional disorders in the brain ranging from delirium and acute psychosis to coma. Astrocytes, the main homeostatic cells of the central nervous system (CNS), play a key role in pathophysiology of neurotoxic insults. We examined the cecal ligation and puncture (CLP) and acetaminophen-induced liver failure (AILF) of Wistar rats, and analysed ultrastructure of astrocytes in the brain cortex and subcortical white matter of sensorimotor zone with transmission electron microscopy. Both models showed significant similarities in reactive changes of astroglial endosomal machinery. In survived animals (with relative prevalence in the CLP-model), at 24 h after intervention we found an increase in number of multivesicular bodies (MVBs) in astroglial perikarya and astroglial processes. In particular, the number of MVBs substantially (3 times of control values) increased in the perivascular astroglial endfeet. Increased number of MVBs in astrocytes was associated with the lesser degree of intracellular oedema and with signs of compensated oedematous tissue changes. In deceased animals, up to 24 h after intervention, single MVBs were localised mainly in astroglial perikarya, and their number was not significantly changed compared to control. Activation of astroglial endosomal-exosomal machinery in both models reflects the uniform pattern of reactive changes of astroglia in these two systemic conditions and may represent activation of astroglial defence in sepsis-associated encephalopathy (SAE) and acute hepatic encephalopathy (AHE). Our data highlight the special role of astroglial adaptive activity in the counterbalancing of an impaired brain homeostasis under action of endogenous toxins. Accumulation of MVBs in astrocytic processes indicates the activation of their intercellular and gliovascular interactions through endo- and exocytosis in SAE and AHE.

全身性炎症以及急性肝功能衰竭引起的内源性毒性会引发大脑中的各种功能障碍，从谵妄和急性精神病到昏迷。星形胶质细胞是中枢神经系统 (CNS) 的主要稳态细胞，在神经毒性损伤的病理生理学中起关键作用。我们检查了 Wistar 大鼠的盲肠结扎和穿刺 (CLP) 和对乙酰氨基酚引起的肝功能衰竭 (AILF)，并用透射电子显微镜分析了大脑皮层和感觉运动区皮层下白质中星形胶质细胞的超微结构。两种模型在星形胶质细胞内体机制的反应性变化方面都表现出显着的相似性。在存活的动物中（在 CLP 模型中相对流行），在干预后 24 小时，我们发现星形胶质细胞周围和星形胶质细胞过程中多泡体 (MVB) 的数量增加。特别是，血管周围星形胶质细胞末端的 MVB 数量显着增加（对照值的 3 倍）。星形胶质细胞中 MVB 数量的增加与较轻的细胞内水肿程度和代偿性水肿组织变化的迹象有关。在死亡动物中，干预后最多 24 小时，单个 MVB 主要位于星形胶质细胞周围，与对照相比，它们的数量没有显着变化。两种模型中星形胶质细胞内体-外泌体机制的激活反映了星形胶质细胞在这两种全身性疾病中反应性变化的统一模式，可能代表脓毒症相关脑病 (SAE) 和急性肝性脑病 (AHE) 中星形胶质细胞防御的激活。我们的数据突出了星形胶质细胞适应性活动在内源性毒素作用下平衡受损脑稳态方面的特殊作用。MVB 在星形胶质细胞过程中的积累表明它们在 SAE 和 AHE 中通过胞内和胞吐作用激活了它们的细胞间和胶质血管相互作用。