Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

Reassembly of the axon initial segment and nodes of Ranvier in regenerated axons of the central nervous system

Myelinated axons of the peripheral and central nervous system（PNS＆CNS）are divided into molecularly distinct excitable domains,including the axon initial segment（AIS）and nodes of Ranvier.The AIS is composed of a dense network of cytoskeletal proteins,cell adhesion molecules,and voltage gated ion channels and is located at the proximal most region of the axon（Koleand Stuart, 2012）.

The engine initiating tissue regeneration:does a common mechanism exist during evolution?

A successful tissue regeneration is a very complex process that requires a precise coordination of many molecular,cellular and physiological events.One of the critical steps is to convert the injury signals into regeneration signals to initiate tissue regeneration.Although many efforts have been made to investigate the mechanisms triggering tissue regeneration,the fundamental questions remain unresolved.One of the major obstacles is that the injury and the initiation of regeneration are two highly coupled processes and hard to separate from one another.In this article,we review the major events occurring at the early injury/regeneration stage in a range of species,and discuss the possible common mechanisms during initiation of tissue regeneration.