Arundic acid (ONO-2506) downregulates neuroinflammation and astrocyte dysfunction after status epilepticus in young rats induced by Li-pilocarpine

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2023-04, Vol.123, p.110704-110704, Article 110704
• Main Authors: Vizuete, Adriana Fernanda K., Leal, Miriara B., Moreira, Ana Paula, Seady, Marina, Taday, Jéssica, Gonçalves, Carlos-Alberto
• Format: Article
• Language: English
• Subjects: Animals; Arundic acid; Astrocyte; Astrocytes - metabolism; Epilepsy; Glial Fibrillary Acidic Protein - metabolism; Hippocampus - metabolism; Neuroinflammation; Neuroinflammatory Diseases; Pilocarpine - toxicity; Rats; S100B; Status epilepticus; Status Epilepticus - chemically induced; Status Epilepticus - drug therapy; Status Epilepticus - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2022.110704

Astrocytes, the most abundant glial cells, have several metabolic functions, including ionic, neurotransmitter and energetic homeostasis for neuronal activity. Reactive astrocytes and their dysfunction have been associated with several brain disorders, including the epileptogenic process. Glial Fibrillary Acidic Protein (GFAP) and S100 calcium-binding protein B (S100B) are astrocyte biomarkers associated with brain injury. We hypothesize that arundic acid (ONO-2506), which is known as an inhibitor of S100B synthesis and secretion, protects the hippocampal tissue from neuroinflammation and astrocyte dysfunction after status epileptics (SE) induction by Li-pilocarpine in young rats. Herein, we investigated the effects of arundic acid treatment, at time points of 6 or 24 h after the induction of SE by Li-pilocarpine, in young rats. In SE animals, arundic acid was able to prevent the damage induced by Li-pilocarpine in the hippocampus, decreasing neuroinflammatory signaling (reducing IL-1β, COX2, TLR4 and RAGE contents), astrogliosis (decreasing GFAP and S100B) and astrocytic dysfunction (recovering levels of GSH, glutamine synthetase and connexin-43). Furthermore, arundic acid improved glucose metabolism and reduced the glutamate excitotoxicity found in epilepsy. Our data reinforce the role of astrocytes in epileptogenesis development and the neuroprotective role of arundic acid, which modulates astrocyte function and neuroinflammation in SE animals. [Display omitted] •Neuroinflammation and astrogliosis are involved in the process of epileptogenesis.•Reactive astrocytes are a potential target for developing new adjunctive drugs to epilepsy treatment.•Arundic acid may have neuroprotective effects, mediated by the inhibition of S100B expression.•Arundic acid had protective effects against neuroinflammation in the SE induced model.•Glial recovery in this model of SE suggests a therapeutic potential of arundic acid.