Arundic Acid (ONO-2506) Attenuates Neuroinflammation and Prevents Motor Impairment in Rats with Intracerebral Hemorrhage.

Autor: Cordeiro JL; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil. ju.julianacordeiro@gmail.com.; Post-Graduation Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-190, Brazil. ju.julianacordeiro@gmail.com., Neves JD; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil., Nicola F; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil., Vizuete AF; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil., Sanches EF; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil.; Post-Graduation Program of Phisiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-190, Brazil., Gonçalves CA; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil., Netto CA; Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2022 Apr; Vol. 42 (3), pp. 739-751. Date of Electronic Publication: 2020 Sep 11.
DOI: 10.1007/s10571-020-00964-6
Abstrakt: Intracerebral hemorrhage (ICH) is a severe stroke subtype caused by the rupture of blood vessels within the brain. Increased levels of S100B protein may contribute to neuroinflammation after ICH through activation of astrocytes and resident microglia, with the consequent production of proinflammatory cytokines and reactive oxygen species (ROS). Inhibition of astrocytic synthesis of S100B by arundic acid (AA) has shown beneficial effects in experimental central nervous system disorders. In present study, we administered AA in a collagenase-induced ICH rodent model in order to evaluate its effects on neurological deficits, S100B levels, astrocytic activation, inflammatory, and oxidative parameters. Rats underwent stereotactic surgery for injection of collagenase in the left striatum and AA (2 μg/μl; weight × 0.005) or vehicle in the left lateral ventricle. Neurological deficits were evaluated by the Ladder rung walking and Grip strength tests. Striatal S100B, astrogliosis, and microglial activation were assessed by immunofluorescence analysis. Striatal levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were measured by ELISA, and the ROS production was analyzed by dichlorofluorescein (DCF) oxidation. AA treatment prevented motor dysfunction, reduced S100B levels, astrogliosis, and microglial activation in the damaged striatum, thus decreasing the release of proinflammatory cytokines IL-1β and TNF-α, as well as ROS production. Taken together, present results suggest that AA could be a pharmacological tool to prevent the harmful effects of increased S100B, attenuating neuroinflammation and secondary brain damage after ICH.
(© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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