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Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampalderived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death.

Curcumin exerts a protective effect in cerebral ischemia through its anti-oxidant and anti-inflammatory activities. γ-enolase is a glycolytic enzyme expressed in neurons that is known to exerts a neuroprotective effect. We investigated whether curcumin regulates γ-enolase expression in focal cerebral ischemic injury in rats. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia. Adult male rats were injected intraperitoneally with either vehicle or curcumin (50 mg/kg) 1 h after MCAO and cerebral cortex tissues were isolated 24 h after MCAO. We found that MCAO-induced injury resulted in a reduction in γ-enolase expression in vehicle-treated animals using a proteomics approach. However, this reduction was attenuated in animals with MCAO treated with curcumin. Reverse-transcription PCR and Western blot analyses also showed that curcumin treatment prevented the MCAO injury-induced reduction in γ-enolase expression. The results of this study suggest that curcumin exerts its neuroprotective function in focal cerebral ischemia by regulating the expression of γ-enolase.

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-3β (GSK-3β) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3β 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-3β, 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-3β, 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-3β/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury.

Protein phosphatase 2A (PP2A) is a serine and threonine protein phosphatase that regulates cell cycle progression and apoptosis. PP2A is composed of various subunits. Among these subunits, subunit B plays an important role in the modulation of PP2A function in the brain. This study investigated PP2A subunit B expression levels after neuronal cell injury. Middle cerebral artery occlusions (MCAO) were surgically induced in adult male rats to induce focal cerebral ischemic injury, and brain tissues were collected 24 h after MCAO. A proteomic approach revealed reduction of PP2A subunit B protein spots in MCAO-operated animals in comparison to sham-operated animals. Western blot analysis confirmed that MCAO induces reductions in PP2A subunit B levels. Moreover, glutamate exposure induces neuronal cell death and leads to reductions of PP2A subunit B levels in a hippocampal-derived cell line. This study demonstrated the decrease of PP2A subunit B in ischemic neuronal cell injury. These results suggest that the decrease of PP2A subunit B after ischemic brain injury can mediate neuronal cell death.