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Updated: Dec 20, 2025
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Arundic Acid (ONO-2506), an Inhibitor of S100B Protein Synthesis, Prevents Neurological Deficits and Brain Tissue
J L Cordeiro1, J D Neves2, A F Vizuete2
1Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Post-graduation Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-190, Brazil.
Insights
Arundic acid (AA) shows promise in treating intracerebral hemorrhage (ICH), a severe stroke type. This study found AA reduced brain damage, improved neurological function, and lowered S100B protein levels in a rat model.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) is a severe stroke subtype with poor outcomes.
- Elevated S100B protein levels correlate with increased injury and neurological deficits after ICH.
- Arundic acid (AA) has shown neuroprotective effects by inhibiting S100B synthesis in other brain injury models.
Purpose of the Study:
- To investigate the neuroprotective effects of intracerebroventricular (ICV) Arundic acid (AA) in an experimental ICH model.
- To assess AA's impact on reactive astrogliosis, S100B levels, antioxidant defenses, cell death, lesion size, and neurological function.
Main Methods:
- Determined effective AA dose by measuring GFAP and S100B levels in non-injured rats.
- Induced ICH in male Wistar rats via intrastriatal collagenase injection.
- Administered 2 μg/μl AA via ICV immediately before ICH induction and evaluated outcomes.
Main Results:
- AA treatment significantly prevented ICH-induced neurological deficits and tissue damage.
- AA inhibited excessive astrocytic activation, cellular apoptosis, and reduced S100B levels centrally and peripherally.
- AA improved neuronal survival and enhanced antioxidant defenses post-ICH.
Conclusions:
- S100B protein is a viable therapeutic target for treating ICH.
- Arundic acid (AA) represents a promising strategy for improving neurological outcomes following experimental brain hemorrhage.
Abstract:
Stroke is one of the leading causes of mortality and neurological morbidity. Intracerebral hemorrhage (ICH) has the poorest prognosis among all stroke subtypes and no treatment has been effective in improving outcomes. Following ICH, the observed high levels of S100B protein have been associated with worsening of injury and neurological deficits. Arundic acid (AA) exerts neuroprotective effects through inhibition of astrocytic synthesis of S100B in some models of experimental brain injury; however, it has not been studied in ICH. The aim of this study was to evaluate the effects of intracerebroventricular (ICV) administration of AA in male Wistar rats submitted to ICH model assessing the following variables: reactive astrogliosis, S100B levels, antioxidant defenses, cell death, lesion extension and neurological function. Firstly, AA was injected at different doses (0.02, 0.2, 2 and 20 μg/μl) in the left lateral ventricle in order to observe which dose would decrease GFAP and S100B striatal levels in non-injured rats. Following determination of the effective dose, ICH damage was induced by IV-S collagenase intrastrial injection and 2 μg/μl AA was injected through ICV route immediately before injury. AA treatment prevented ICH-induced neurological deficits and tissue damage, inhibited excessive astrocytic activation and cellular apoptosis, reduced peripheral and central S100B levels (in striatum, serum and cerebrospinal fluid), improved neuronal survival and enhanced the antioxidant defences after injury. Altogether, these results suggest that S100B is a viable target for treating ICH and highlight AA as an interesting strategy for improving neurological outcome after experimental brain hemorrhage.
