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Review
. 2018;16(9):1314-1319.
doi: 10.2174/1570159X15666171123200646.

Autophagy after Subarachnoid Hemorrhage: Can Cell Death be Good?

Wing-Mann Ho  1   2 , Onat Akyol  2 , Haley Reis  3 , Cesar Reis  4 , Devin McBride  2 , Claudius Thome  1 , John Zhang  2
Affiliations
Review

Autophagy after Subarachnoid Hemorrhage: Can Cell Death be Good?

Wing-Mann Ho et al. Curr Neuropharmacol. 2018.

Abstract

Background: Autophagy is a prosurvival, reparative process that maintainsww cellular homeostasis through lysosomal degradation of selected cytoplasmic components and programmed death of old, dysfunctional, or unnecessary cytoplasmic entities. According to growing evidence, autophagy shows beneficial effects following subarachnoid hemorrhage (SAH). SAH is considered one of the most devastating forms of stroke.

Methods: In this review lies in revealing the pathophysiological pathways and the effects of autophagy. Current results from animal studies will be discussed focusing on the effects of inhibitors and inducers of autophagy. In addition, this review discusses the clinical translation of potential neuropharmacological targets that can help prevent early brain injury (EBI) following SAH by incorporating programmed cell death into clinical management.

Results: Published data showed that autophagy mechanisms have a prosurvival effect to reduce apoptotic cell death after SAH. However, if SAH exceeds a certain stress threshold, autophagy mechanisms lead to increased apoptotic cell death, more brain injury, and worse outcome.

Conclusion: Future investigation on the differences and molecular switches between protective mechanisms of autophagy and excessive "self-eating" autophagy leading to cell death is needed to achieve more insight into the complex pathophysiology of brain injury after SAH. If autophagy after SAH can be controlled to lead to beneficial effects only, as the physiological self-control mechanism, this could be an important target for treatment.

Keywords: Subarachnoid hemorrhage; autophagosome; autophagy; brain injury; cell death; lysosome; neuroprotection..

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Figures

Fig. (1)
Fig. (1)
Autophagy pathways after SAH. Major mechanisms of after SAH are cellular hypoxia and starvation leading to activation of the Nrf-2, Bcl-2, ROS, and inhibition of mTOR activity. Autophagy is initiated via ULK complex induced autophagosome membrane nucleation through PI3K. Elongation and maturation of the phagophore forms the autophagosome. Once the autophagic vesicles are formed and cargo is engulfed, the autophagosome is fused with the lysosome. Unlike this form of chaperone-mediated macroautophagy, there is direct lysosomal microautophagy.
See this image and copyright information in PMC

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