Knockout of transient receptor potential ankyrin 1 (TRPA1) modulates the glial phenotype and alleviates perihematomal neuroinflammation after intracerebral hemorrhage in mice via MAPK/NF-κB signaling

The objective is to explore the role of astrocytic transient receptor potential ankyrin 1 (TRPA1) in glial phenotype transformation in neuroinflammation after intracerebral hemorrhage (ICH). Wild-type astrocytes and TRPA1(-/-) astrocytes were subjected to 6-h hemin treatment, and the calcium ions and transcriptome sequencing were assessed. A mouse autologous blood injection ICH model was established to evaluate the proliferation and phenotypes of astrocytes and microglia around the hematoma. The neuroinflammation and behavioral performance of wild-type ICH mice and TRPA1(-/-) ICH mice were assessed. Knockout of astrocytic TRPA1 decreased calcium ions of astrocytes after hemin treatment in-vitro, and microglial and astrocytes around the hematoma proliferated after the ICH model. Furthermore, RNA-sequencing (RNA-seq), immunofluorescence, and Western blotting results showed that the activated astrocytes transformed into the A2 phenotype in TRPA1(-/-) ICH mice. The 'ameboid' microglia were observed around the hematoma in TRPA1(-/-) ICH mice. The proliferation of A2 astrocytes and 'ameboid' microglia ameliorated the neuroinflammation after ICH. The inflammatory response was reduced by inhibiting the mitogen-activated protein kinase/nuclear factor kappa-B signaling pathway, and neurologic deficits were improved in TRPA1(-/-) ICH mice compared with wild-type ICH mice. This research suggests that astrocytic TRPA1 is a new therapeutic target to rescue neuroinflammation by modulating the glial phenotype after ICH.

Automated summary

This study investigates the role of astrocytic transient receptor potential ankyrin 1 (TRPA1) in glial phenotype transformation in neuroinflammation after intracerebral hemorrhage (ICH). The results show that knockout of astrocytic TRPA1 decreases calcium ions of astrocytes and promotes proliferation and phenotypic transformation of astrocytes and microglia. Inhibiting the mitogen-activated protein kinase/nuclear factor kappa-B signaling pathway reduces neuroinflammation and improves neurological deficits. Therefore, astrocytic TRPA1 is a potential therapeutic target for rescuing neuroinflammation after ICH through modulation of glial phenotype.