In:
NeuroReport, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 2 ( 2023-02-1), p. 81-92
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0959-4965
DOI:
10.1097/WNR.0000000000001862
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
2031485-1
