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Neurobiol Dis. 2019 Feb;122:9-15. doi: 10.1016/j.nbd.2018.04.018. Epub 2018 Apr 26.

The role of autophagy in acute brain injury: A state of flux?

Author information

1
Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
2
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.
3
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; Brain Care Institute, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
4
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; Brain Care Institute, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address: clarkrs@upmc.edu.

Abstract

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.

KEYWORDS:

Autophagic flux; Cerebral ischemia; Hypoxia-ischemic brain injury; Traumatic brain injury

PMID:
29704549
PMCID:
PMC6203674
[Available on 2020-02-01]
DOI:
10.1016/j.nbd.2018.04.018

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