Autophagy in acute brain injury: Feast, famine, or folly?

► Autophagy is a vital homeostatic process and disruption of autophagy in brain for long durations (as yet unknown, how long) is detrimental. ► Increased autophagy is observed in multiple and distinct experimental models of brain injury including trauma, hypoxia-ischemia, status epilepticus, and subarachnoid hemorrhage. ► Whether increased autophagy in brain in response to injury is in-and-of-itself a homeostatic response, additive cellular stress (in essence “autophagic stress”), a direct process of neurodegeneration and cell death, or merely a non-contributory consequence of brain damage produced by these insults remains uncertain and controversial. ► It is possible that the circumstances of manipulating autophagy after brain injury are dependent upon the cell's capacity to respond in relation to the cumulative burden of damaged or dysfunctional macromolecules and organelles.