Protective Effect of Nervonic Acid Against 6-Hydroxydopamine-Induced Oxidative Stress in PC-12 Cells.

Increased oxidative stress in the human brain is observed in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD), and is considered to be a major cause of progression of these disease states. A very long-chain fatty acid, nervonic acid (NA), is the main fatty acid found in various sphingolipid species in the central nervous system. NA plays an important role in forming the plasma membrane's lipid bilayer and in maintaining normal myelin function. In this study, we examined the neuroprotective effect of NA against rat pheochromocytoma (PC-12) cells stimulated by 6-hydroxydopamine (6-OHDA), which served as a cell model of PD. PC-12 cells were pre-treated with different concentrations of NA for 48 h then subsequently co-treated with NA and 6-OHDA for 48 h to induce cellular oxidative stress. Cell viability was significantly increased by pre-treatment with a very low concentration of NA. The level of malondialdehyde, a marker of lipid peroxidation, was significantly decreased in NA-treated cells. The expression levels of superoxide dismutases (Mn SOD and Cu/Zn SOD) and γ-glutamylcysteine synthetase (GCLC), responsible for the synthesis of glutathione, were significantly increased, indicating that pre-treatment with NA activated the cellular antioxidant defense system. These results suggest that NA may play a role as a neuroprotective mediator in the brain.

Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy.

Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE), and aquaporin 4 (AQP4) plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg) treated group than in the nontreated (saline) group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function.