Unveiling microglia heterogeneity in intracerebral hemorrhage.

Microglia are important innate immune cells in the brain, and a rich diversity of subtypes has recently been discovered that expand beyond the traditional classification of traditional M1 (pro-inflammatory) and M2 (anti-inflammatory) classifications. Intracerebral hemorrhage (ICH) is a devastating form of stroke, and the understanding of its later-stage pathological mechanisms remains incomplete. In this study, through the analysis of single-cell transcripts from mice brains 14 days post-ICH, three disease-associated expression patterns of microglia were identified. These include a lipid metabolism and phagocytosis phenotype reminiscent of Disease-Associated Microglia (DAM) initially discovered in Alzheimer's disease models, a phenotype associated with angiogenesis, and a relatively independent phenotype similar to the pro-inflammatory M1 state. These findings were further validated through immunofluorescence in both mouse and human specimens. In addition, analysis of single-cell transcripts from mice brains 3 days post-ICH suggested that microglia involved in lipid metabolism and phagocytosis likely emerge from early proliferating populations. Given the distinct origins and phenotypic characteristics of pro-inflammatory and reparative microglia, interventions targeting these cells hold the potential to modulate the delicate balance between injury and repair during the pathophysiological process of ICH, highlighting a pivotal direction for future therapeutic strategies.

Norad Competently Binds with Pum2 to Regulate Neuronal Apoptosis and Play a Neuroprotective Role After SAH in Mice.

Subarachnoid Hemorrhage (SAH) is a cerebrovascular disorder that has been found to have severe consequences, including a high mortality and disability rate. Research has indicated that neuronal death, particularly apoptosis, plays a major role in the neurological impairment that follows SAH. RNA-binding protein Pum2 can interfere with translation or other biological functions by connecting to the UGUAHAUA sequence on RNA. Noncoding RNA activated by DNA damage (Norad) contains some Pum2 recognition sequences, which may bind to Pum2 protein and affect its capacity to attach to target mRNA. The time course expression of Norad and Pum2 after SAH is analyzed by establishing a mouse SAH model. Subsequently, the purpose of this study is to investigate the potential role and mechanism of the Norad-Pum2 axis after SAH using lentivirus overexpression of Pum2 and knockdown of Norad. Analysis of Pum2 and Norad levels reveal that the former is significantly reduce and the latter is significantly increased in the SAH group compared to the sham group. Subsequent overexpression of Pum2 and Norad knockdown is found to reduce SAH-induced oxidative stress, neuronal apoptosis, and ultimately improve behavioral and cognitive changes in SAH mice. Our study indicates that Norad-Pum2 acts as a neuromodulator in SAH, and that by increasing Pum2 and decreasing Norad levels, SAH-induced neuronal apoptosis can be reduced and neurological deficits alleviated. Consequently, Norad-Pum2 may be a promising therapeutic target for SAH.