# Decanoic acid modulates cerebral metabolism and attenuates ischemic injury in a mouse model

## TL;DR

Decanoic acid, a fatty acid, reduces brain injury and improves recovery in mice after a stroke by protecting against oxidative stress and inflammation.

## Contribution

This study demonstrates decanoic acid's neuroprotective effects through metabolic modulation and anti-inflammatory action in a mouse model of cerebral ischemia.

## Key findings

- Decanoic acid reduced infarct volume and improved motor and memory performance in mice.
- Treatment restored lipid and aldehyde homeostasis and reduced oxidative stress and inflammation.
- DA modulated ischemia-induced metabolic disturbances and reversed pro-inflammatory cytokine elevation.

## Abstract

Cerebral ischemia, resulting from acute interruption of cerebral blood flow, is a leading cause of long-term cognitive and motor disabilities, and current therapeutic options remain limited. Decanoic acid, a medium-chain fatty acid with antioxidant and anti-inflammatory properties, has been proposed as a potential neuroprotective agent. This study evaluated the neuroprotective and metabolic effects of decanoic acid in a murine model of permanent middle cerebral artery occlusion (MCAO). Male mice received decanoic acid (62.5, 125, or 250 mg/kg, oral gavage) or vehicle for 7 days after MCAO. Infarct volume was quantified by TTC staining. Motor and cognitive performance were assessed using the Cylinder, Limb Clasping, Object Location, and Novel Object Recognition tests. Metabolomic profiling (HS/GC–MS) of cortical tissue was performed to characterize ischemia-induced metabolic disturbances and treatment-related modulation of lipid and energy metabolism. Oxidative stress markers, antioxidant enzyme activities, and inflammatory cytokines (ELISA) were also measured in brain tissue. Decanoic acid significantly reduced total infarct volume and improved motor coordination and memory performance. Metabolomic analysis revealed that DA modulated metabolites disrupted by ischemia, partially restoring lipid and aldehyde homeostasis. Furthermore, treatment decreased lipid peroxidation, enhanced antioxidant enzyme activities, and effectively reversed the ischemia-induced elevation of pro-inflammatory cytokines, thereby neutralizing the neuroinflammatory response. These findings suggest that decanoic acid may exert a coordinated regulatory effect, contributing to neuroprotection through the modulation of cerebral metabolic homeostasis and attenuation of oxidative and inflammatory stress, and supporting its potential as a therapeutic candidate for ischemic brain injury.

The online version contains supplementary material available at 10.1007/s11011-026-01832-w.