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

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

  • Prog Neuropsychopharmacol Biol Psychiatry. 2023 Apr 20:123:110704. doi: 10.1016/j.pnpbp.2022.110704.
Adriana Fernanda K Vizuete 1,  Miriara B Leal 2,  Ana Paula Moreira 2,  Marina Seady 2,  Jéssica Taday 2,  Carlos-Alberto Gonçalves 2
Affiliations

Affiliations

  • 1 Laboratory of Calcium-Binding Proteins in CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Pos Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, RS, Brazil. Electronic address: [email protected].
  • 2 Laboratory of Calcium-Binding Proteins in CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Pos Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, RS, Brazil.
PMID: 36565981 DOI: 10.1016/j.pnpbp.2022.110704
Abstract

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.

Keywords

Arundic acid; Astrocyte; Neuroinflammation; S100B; Status epilepticus.

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