Neuroprotective effects of oleic acid in rodent models of cerebral ischaemia.
Jungbin SongYoung-Sik KimDong Hwan LeeSung Hyun LeeHyo Jin ParkDong-Hun LeeHocheol KimPublished in: Scientific reports (2019)
Oleic acid (OA) is released from brain phospholipids after cerebral ischaemia; however, its role in ischaemic injury remains unknown. We hypothesised that OA has neuroprotective effects after cerebral ischaemia, which may be exerted through peroxisome proliferator-activated receptor gamma (PPAR-γ) activation, since OA is an endogenous ligand of PPAR-γ. The effects of OA administration were evaluated in rodent models of middle cerebral artery occlusion (MCAO), photothrombosis, and four-vessel occlusion (4-VO). We determined the time window of therapeutic opportunity and examined the ability of the PPAR-γ antagonist GW9662 to reverse OA's protective effects after MCAO. We found that OA administration decreased the MCAO-induced infarct volume and functional deficits, photothrombosis-induced infarct volume, and 4-VO-induced hippocampal neuronal death. Additionally, OA was highly efficacious when administered up to 3 h after MCAO. Pre-treatment with GW9662 abolished the inhibitory effects of OA on the infarct volume and immunoreactivity of key inflammatory mediators in the ischaemic cortex. Our results indicate that OA has neuroprotective effects against transient and permanent focal cerebral ischaemia, as well as global cerebral ischaemia. It may have therapeutic value for the ischaemic stroke treatment with a clinically feasible therapeutic window. The OA-mediated neuroprotection might be attributable to its anti-inflammatory actions through PPAR-γ activation.
Keyphrases
- knee osteoarthritis
- cerebral ischemia
- subarachnoid hemorrhage
- middle cerebral artery
- insulin resistance
- high glucose
- brain injury
- diabetic rats
- fatty acid
- acute myocardial infarction
- anti inflammatory
- heart failure
- adipose tissue
- drug induced
- endothelial cells
- atrial fibrillation
- skeletal muscle
- percutaneous coronary intervention