Lab Anim Res.  2012 Dec;28(4):273-278. 10.5625/lar.2012.28.4.273.

Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia

• Koh PO

• KMID: 1431411
• DOI: http://doi.org/10.5625/lar.2012.28.4.273

Abstract

Nitric oxide (NO) is generated by three different NO synthase (NOS) isoforms, endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). It is known that eNOS produces NO, which exerts a protective effect, while iNOS produces NO with neurotoxic effects. Ferulic acid preserves neuronal cells against from cerebral ischemia and glutamate-induced excitotoxicity. This study confirmed the neuroprotective effect of ferulic acid and investigated the levels of three NOS isoforms in focal cerebral ischemia with or without ferulic acid. Rats were immediately treated with ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were collected at 24 h after the onset of occlusion. The expressions of these three isoforms in cerebral ischemia with ferulic acid were analyzed using Western blot technique. Ferulic acid treatment significantly decreases the number of TUNEL-positive cells in the cerebral cortex against MCAO injury. The levels of eNOS decreased in MCAO-operated animals, while ferulic acid treatment attenuated the MCAO-induced decrease of eNOS. However, iNOS and nNOS expression levels increased during MCAO, and ferulic acid prevented injury-induced increase of these isoforms. Thus, these findings suggest that the up- and down modulation of three isoforms by ferulic acid is associated with a neuroprotective mechanism.

Keyword

Ferulic acid; neuroprotection; NOS

MeSH Terms

Animals
Blotting, Western
Brain
Brain Ischemia
Cerebral Cortex
Coumaric Acids
Infarction, Middle Cerebral Artery
Neurons
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Protein Isoforms
Rats
Coumaric Acids
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Protein Isoforms

Figure

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  Figure 1 Representative photos of TUNEL staining in the cerebral cortex from vehicle+MCAO (A), ferulic acid+MCAO (B), vehicle+sham (C), ferulic acid+sham (D) animals. Ferulic acid treatment attenuates the number of TUNEL-positive cells in MCAO-operated animals. Arrows indicate the positive cells of TUNEL staining. Scale bar=100 µm. Apoptotic index indicate the percentage of TUNEL-positive cells in the ischemic regions (E). Data (n=5) are represented as mean±S.E.M. *P<0.01.

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  Figure 2 Western blot analysis of eNOS in the cerebral cortex from vehicle+MCAO, ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as a ratio, proteins intensity to actin intensity. Molecular weight (kDa) are depicted at right. Data (n=5) are represented as mean±S.E.M. *P<0.05.

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  Figure 3 Western blot analysis of iNOS in the cerebral cortex from vehicle+MCAO, ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as a ratio, proteins intensity to actin intensity. Molecular weight (kDa) are depicted at right. Data (n=5) are represented as mean±S.E.M. *P<0.05.

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  Figure 4 Western blot analysis of nNOS in the cerebral cortex from vehicle+MCAO, ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as a ratio, proteins intensity to actin intensity. Molecular weight (kDa) are depicted at right. Data (n=5) are represented as mean±S.E.M. *P<0.05.

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