Ferulic acid prevents the injury-induced decrease of gamma-enolase expression in brain tissue and HT22 cells / 한국실험동물학회지

Ferulic acid is known to act as a protective agent in cerebral ischemia through its anti-oxidant activity. gamma-Enolase is a neuron-specific enolase that also exerts a neuroprotective effect. Here, we investigated whether ferulic acid regulates the expression level of gamma-enolase in middle cerebral artery occlusion (MCAO)-induced brain injury and glutamate exposure-induced neuronal cell death. Adult male rats were treated with either vehicle or ferulic acid (100 mg/kg, i.v.) after MCAO and cerebral cortex tissues were collected 24 h after MCAO. Using a proteomics approach, we found that gamma-enolase expression was decreased in MCAO-injured animals treated with vehicle alone, whereas ferulic acid treatment attenuated this decrease. Reverse-transcription PCR and Western blot analyses confirmed that ferulic acid treatment prevented MCAO injury-induced decrease in gamma-enolase. Furthermore, in hippocampal-derived cell lines, glutamate exposure also decreased gamma-enolase expression and ferulic acid treatment attenuated this glutamate-induced decrease in gamma-enolase. These findings suggest that ferulic acid mediates a neuroprotective effect by attenuating injury-induced decreases of gamma-enolase expression in neuronal cells.

Ferulic acid regulates the AKT/GSK-3beta/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model / 한국실험동물학회지

Ferulic acid, a component of the plants Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, exerts a neuroprotective effect by regulating various signaling pathways. This study showed that ferulic acid treatment prevents the injury-induced increase of collapsin response mediator protein 2 (CRMP-2) in focal cerebral ischemia. Glycogen synthase kinase-3beta (GSK-3beta) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3beta is inactivated by phosphorylation by Akt. This study investigated whether ferulic acid modulates the expression of CRMP-2 and its upstream targets, Akt and GSK-3beta, in focal cerebral ischemia. Male rats were treated immediately with ferulic acid (100 mg/kg, i.v.) or vehicle after middle cerebral artery occlusion (MCAO), and then cerebral cortices were collected 24 hr after MCAO. MCAO resulted in decreased levels of phospho-Akt and phospho-GSK-3beta, while ferulic acid treatment prevented the decrease in the levels of these proteins. Moreover, phospho-CRMP-2 and CRMP-2 levels increased during MCAO, whereas ferulic acid attenuated these injury-induced increases. These results demonstrate that ferulic acid regulates the Akt/GSK-3beta/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury.

Focal cerebral ischemic injury decreases calbindin expression in brain tissue and HT22 cells / 한국실험동물학회지

Calbindin is a calcium binding protein that controls intracellular calcium levels and has a neuroprotective function against apoptotic stimuli. We investigated the expression of calbindin in ischemic brain injury. Focal cerebral ischemia was induced in male rats by middle cerebral artery occlusion (MCAO) and cerebral cortices were collected 24 h after MCAO. Cerebral ischemia significantly increased infarct volume. RT-PCR and Western blot analyses showed that MCAO injury induced a decrease of calbindin expression. Moreover, immunohistochemical staining showed that the number of calbindin-positive cells decreased in ischemic regions of MCAO-operated animals. In cultured hippocampal-derived cell lines, glutamate exposure increased intracellular Ca2+ concentrations and decreased calbindin expression. Taken together, both in vivo and in vitro results demonstrated decreases of calbindin after neuronal cell injury. These results suggest that decreases of calbindin in ischemic brain injury contribute to neuronal cell death.