Acta Pharmacologica Sinica 2006 February; 27 (2): 145-150; doi: 10.1111/j.1745-7254.2006.00259.x

Aim: To observe the effects of stearic acid, a long-chain saturated fatty acid consisting of 18 carbon atoms, on brain (cortical or hippocampal) slices insulted by oxygen-glucose deprivation (OGD), glutamate or sodium azide (NaN₃) in vitro.

Methods: The activities of hippocampal slices were monitored by population spikes recorded in the CA1 region. In vitro injury models of brain slice were induced by 10 min of OGD, 1 mmol/L glutamate or 10 mmol/L NaN₃. After 30 min of pre-incubation with stearic acid (3-30 µmol/L), brain slices (cortical or hippocampal) were subjected to OGD, glutamate or NaN₃, and the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. MK886 [5 mmol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR-a)] or BADGE (bisphenol A diglycidyl ether; 100 µmol/L; an antagonist of PPAR-γ) were tested for their effects on the neuroprotection afforded by stearic acid.

Results: Viability of brain slices was not changed significantly after direct incubation with stearic acid. OGD, glutamate and NaN₃ injury significantly decreased the viability of brain slices. Stearic acid (3-30 µmol/L) dose-dependently protected brain slices from OGD and glutamate injury but not from NaN₃ injury, and its neuroprotective effect was completely abolished by BADGE.

Conclusion: Stearic acid can protect brain slices (cortical or hippocampal) against injury induced by OGD or glutamate. Its neuroprotective effect may be mainly mediated by the activation of PPAR-γ.

Keywords: fatty acid; brain slices; ischemia; glutamate; energy metabolism