Brain Cell Senescence: A New Therapeutic Target for the Acute Treatment of Ischemic Stroke.
J Neuropathol Exp Neurol
; 81(8): 614-620, 2022 07 19.
Article
en En
| MEDLINE
| ID: mdl-35763058
ABSTRACT
Aging is a major risk factor for cerebral infarction. Since cellular senescence is intrinsic to aging, we postulated that stroke-induced cellular senescence might contribute to neural dysfunction. Adult male Wistar rats underwent 60-minute middle cerebral artery occlusion and were grouped according to 3 reperfusion times 24 hours, 3, and 7 days. The major biomarkers of senescence 1) accumulation of the lysosomal pigment, lipofuscin; 2) expression of the cell cycle arrest markers p21, p53, and p16INK4a; and 3) expression of the senescence-associated secretory phenotype cytokines interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) were investigated in brain samples. Lipofuscin accumulation was scarce at the initial stage of brain damage (24 hours), but progressively increased until it reached massive distribution at 7 days post-ischemia. Lipofuscin granules (aggresomes) were mainly confined to the infarcted areas, that is parietal cortex and adjacent caudate-putamen, which were equally affected. The expression of p21, p53, and p16INK4a, and that of IL-6, TNF-α, and IL-1ß, was significantly higher in the ischemic hemisphere than in the non-ischemic hemisphere. These data indicate that brain cell senescence develops during acute ischemic infarction and suggest that the acute treatment of ischemic stroke might be enhanced using senolytic drugs.
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Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Isquemia Encefálica
/
Accidente Cerebrovascular
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Accidente Cerebrovascular Isquémico
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
2022
Tipo del documento:
Article