Mechanisms and Therapeutic Targets of Depression After Intracerebral Hemorrhage.

The relationship between depression and intracerebral hemorrhage (ICH) is complicated. One of the most common neuropsychiatric comorbidities of hemorrhagic stroke is Post-ICH depression. Depression, as a neuropsychiatric symptom, also negatively impacts the outcome of ICH by enhancing morbidity, disability, and mortality. However, the ICH outcome can be improved by antidepressants such as the frequently-used selective serotonin reuptake inhibitors. This review therefore presents the mechanisms of post-ICH depression, we grouped the mechanisms according to inflammation, oxidative stress (OS), apoptosis and autophagy, and explained them through their several associated signaling pathways. Inflammation is mainly related to Toll-like receptors (TLRs), the NF-kB mediated signal pathway, the PPAR-γ-dependent pathway, as well as other signaling pathways. OS is associated to nuclear factor erythroid-2 related factor 2 (Nrf2), the PI3K/Akt pathway and the MAPK/P38 pathway. Moreover, autophagy is associated with the mTOR signaling cascade and the NF-kB mediated signal pathway, while apoptosis is correlated with the death receptor-mediated apoptosis pathway, mitochondrial apoptosis pathway, caspase-independent pathways and others. Furthermore, we found that neuroinflammation, oxidative stress, autophagy, and apoptosis experience interactions with one another. Additionally, it may provide several potential therapeutic targets for patients that might suffer from depression after ICH.