Tristetraprolin attenuates brain edema in a rat model of cerebral hemorrhage

Abstract

Objectives We evaluated the protective effects of protein phosphatase 2A (PP2A)/tristetraprolin (TTP) against brain edema in a rat model of cerebral hemorrhage, bleeding in the brain that occurs in tissues and ventricles. TTP is a well‐known mRNA‐binding protein and essential regulatory molecule for gene expression. Methods Cerebral hemorrhage was induced in male albino rats divided into four homogeneous groups: normal control (I), control (II), PP2A siRNA (III), and scrambled siRNA (IV). Neurological scores, caspase‐3 mRNA and protein expression, PP2A and TTP protein expression, apoptosis, and water content in the brain were determined. Results The neurological score decreased substantially to 8.2 in rats in which cerebral hemorrhage was induced and was further reduced to 7.4 and 7.7 in groups III and IV, respectively. Caspase‐3 expression increased significantly by 90% in group II and by 26.9% in group III. Apoptosis increased by 26.1% in rats in which cerebral hemorrhage was induced and increased considerably by 35.3% and 33.4% in groups III and IV, respectively. PP2A and TTP protein expression increased significantly by 87% and 59%, as compared to their respective sham controls. However, PP2A and TTP siRNA treatment reduced the protein expression of PP2A and TTP in groups III and IV. The water content in the brain increased significantly by 77.4% in rats in which cerebral hemorrhage was induced (group II), as compared to the sham group. The water content in the brain increased by 84.1% and 78.7% in groups III and IV, respectively. Conclusion Taken together, these data indicate that TTP has a protective role against brain edema by reducing inflammation, apoptosis, and water content in the brain at 48 hr after cerebral hemorrhage. Our findings may be useful for developing important approaches to treating brain injury.

Stress Granule-Related Genes during Embryogenesis of an Invertebrate Chordate

“…Our data, indicating the activity of cr-ttp promoter in the neural plate of the mid-gastrula embryos, suggest the involvement of TTP in the development of the ascidian brain. This observation agrees with the reported transcriptional activity of G3BP2, TIAR and TTP in the mammalian brain, likely implicated in both signal transduction and RNA-metabolism (Kennedy et al, 2001; Rayman and Kandel, 2017; Li et al, 2019). The activity of the promoter in brain precursors is increased by metal exposure in both the mid-gastrula and mid tailbud II embryos: this suggests a decisive role of these genes in controlling cell homeostasis and facing stressful conditions.…”