Correction: Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis

Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH. Analysis of the molecular processes involved in the progression of hemorrhage-induced brain damage has yielded a potential therapeutic target. Fei Liu and Aihua Liu at the Central South University in Changsha, China, and co-workers examined mechanisms behind the extensive brain damage that can be caused by subarachnoid hemorrhage, bleeding in a space between the brain and its surrounding membranes. In experiments on human samples and rat models, the researchers showed that the TDP-43 protein was over-expressed in cerebrospinal fluid after hemorrhage, and that the build-up of this protein aggravated nerve cell damage and dysfunction. TDP-43 is regulated by a pathway involving a potent enzyme involved in regulation of gene expression called HDAC1. Treatment of rat models with an HDAC1 inhibitor degraded TDP-43 and limited the progression of brain damage.