Significance: Autophagy and apoptosis are two important cellular mechanisms behind brain injuries, which are severe clinical situations with increasing incidences worldwide. To search for more and better treatments for brain injuries, it is essential to deepen the understanding of autophagy, apoptosis, and their interactions in brain injuries. This article first analyzes how autophagy and apoptosis participate in the pathogenetic processes of brain injuries respectively and mutually, then summarizes some promising treatments targeting autophagy and apoptosis to show the potential clinical applications in personalized medicine and precision medicine in the future. Recent Advances: Most current studies suggest that apoptosis is detrimental to brain recovery. Several studies indicate that autophagy can cause unnecessary death of neurons after brain injuries, while others show that autophagy is beneficial for acute brain injuries (ABIs) by facilitating the removal of damaged proteins and organelles. Whether autophagy is beneficial or detrimental in ABIs depends on many factors, and the results from different research groups are diverse or even controversial, making this topic more appealing to be explored further. Critical Issues: Neuronal autophagy and apoptosis are two primary pathological processes in ABIs. How they interact with each other and how their regulations affect the outcome and prognosis of brain injuries remain uncertain, making these answers more critical. Future Directions: Insights into the interplay between autophagy and apoptosis and the accurate regulations of their balance in ABIs may promote personalized and precise treatments in the field of brain injuries. Antioxid. Redox Signal. 38, 234-257.
Keywords: acute brain injuries; apoptosis; autophagy; treatment.