Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA 15219, USA; Brain Care Institute, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Neurobiol Dis. 2019 Feb;122:9-15. doi: 10.1016/j.nbd.2018.04.018. Epub 2018 Apr 26.
It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury.
研究表明，在多种急性脑损伤后，包括创伤、局灶性和全脑缺血后，自噬会明显增加。然而，仍有争议的是，脑内自噬的这种增强检测是代表一种动态平衡或病理过程，还是一种伴随现象。急性脑损伤后自噬的最终作用可能取决于：1）脑损伤的程度和整体自噬负担；2）单个细胞类型增加自噬通量的能力；3）局部氧化还原状态和并行细胞死亡途径的信号转导；4）消除细胞内外损伤相关分子模式和有毒蛋白质及代谢物的能力；以及 5）促自噬或抗自噬干预的时机。在这篇综述中，我们试图调和支持自噬在急性脑损伤模型中具有有益和有害作用的相互矛盾的研究。
