Prevention of Glutamate Accumulation and Upregulation of Phospho-Akt may Account for Neuroprotection Afforded by Bergamot Essential Oil against Brain Injury Induced by Focal Cerebral Ischemia in Rat.
The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on brain damage caused by permanent focal cerebral ischemia in rat were investigated. Administration of BEO (0.1-0.5 ml/kg but not 1 ml/kg, given intraperitoneally 1 h before occlusion of the middle cerebral artery, MCAo) significantly reduced infarct size after 24 h permanent MCAo. The most effective dose (0.5 ml/kg) resulted in a significant reduction of infarct extension throughout the brain, especially in the medial striatum and the motor cortex as revealed by TTC staining of tissue slices. Microdialysis experiments show that BEO (0.5 ml/kg) did not affect basal amino acid levels, whereas it significantly reduced excitatory amino acid, namely aspartate and glutamate, efflux in the frontoparietal cortex typically observed following MCAo. Western blotting experiments demonstrated that these early effects were associated, 24 h after permanent MCAo, to a significant increase in the phosphorylation and activity of the prosurvival kinase, Akt. Indeed, BEO significantly enhanced the phosphorylation of the deleterious downstream kinase, GSK-3beta, whose activity is negatively regulated via phosphorylation by Akt.
Amantea
Diana
D
Department of Pharmacobiology and Center of Neuropharmacology of Normal and Pathological Neuronal Plasticity, UCADH, University of Calabria, 87036 Cosenza, Italy.
Fratto
Vincenza
V
Maida
Simona
S
Rotiroti
Domenicantonio
D
Ragusa
Salvatore
S
Nappi
Giuseppe
G
Bagetta
Giacinto
G
Corasaniti
Maria Tiziana
MT
D000818:Animals; D020520:Brain Infarction / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000096:biosynthesis*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009822:Oils, Volatile / Q000627:therapeutic use*; D010938:Plant Oils / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
D018696:Neuroprotective Agents; D009822:Oils, Volatile; D010938:Plant Oils; C068336:bergamot oil; D018698:Glutamic Acid; D051057:Proto-Oncogene Proteins c-akt