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  • Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum.

Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum.

PloS one (2019-03-12)
Tadasuke Tominaga, Ryo Shimada, Yoshikazu Okada, Takakazu Kawamata, Kazuhiko Kibayashi
ABSTRACT

Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein Rat mAb (2.2B10), liquid, clone 2.2B10, Calbiochem®
Sigma-Aldrich
Anti-NeuN Antibody, serum, from guinea pig