Role of Central Nervous System Periostin in Cerebral Ischemia

Abstract

Background and Purpose-Although periostin, an extracellular matrix glycoprotein, plays pivotal roles in survival, migration, and regeneration in various cells, its expression and function in the brain are still unknown. Here, we investigated the expression and role of periostin in the ischemic brain. Methods-Expression of full-length periostin (periostin 1 [Pn1]) and its splicing variant lacking exon 17 (periostin 2 [Pn2]) was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining in male C57BL6/J mice. The actions of periostin were examined in adult primary neuronal culture and in a transient middle cerebral artery occlusion (tMCAo) model. Results-Expression of Pn2, but not of Pn1, mRNA was markedly changed after tMCAo. Pn2 mRNA was decreased in the ischemic core at 3 hours after ischemia. At 24 hours, Pn2 mRNA was significantly increased in both the peri-ischemic and ischemic regions. Periostin was mainly observed in neurons in normal brain. However, neuronal expression of periostin was decreased temporarily in the ischemic region, but increased in astrocytes and around endothelial cells at 24 hours after tMCAo. Of importance, intracerebroventricular injection of Pn2 resulted in a significant reduction in infarct volume at 24 hours after tMCAo associated with phosphorylation of Akt. Also, the Pn2-treated mice survived longer until 1 week after tMCAo. Pn2 significantly inhibited neuronal death under hypoxia and stimulated neurite outgrowth. Conclusions-Here, we demonstrated that periostin was expressed in the brain, and exogenous Pn2 exhibited neuroprotective effects and accelerated neurite outgrowth. Additional studies on periostin may provide new insights into the treatment of ischemic stroke. (Stroke. 2012;43:1108-1114.)Key Words: periostin Ⅲ ischemia Ⅲ neuroprotection Ⅲ extracellular matrix Ⅲ neurite outgrowth P eriostin is a 93-kDa secreted N-glycoprotein that modulates cell-matrix interactions and cell functions in the extracellular matrix (ECM). 1 Although periostin was originally found in osteoblasts, 2 recent studies showed that periostin plays pivotal roles in cell survival under hypoxic conditions, 3 migration of cancer cells, 4 and proliferation of cardiomyocytes after acute myocardial infarction. 5 Interestingly, periostin has homology with fasciclin I, which is expressed in grasshoppers and Drosophila. Fasciclin I is a cell adhesion molecule expressed in the central nervous system (CNS) during embryonic CNS development in Drosophila. 6 Also, laser inactivation of fasciclin I disrupts axon adhesion of grasshopper pioneer neurons. 7 Thus, periostin might have pivotal roles in the CNS in mammals, although its expression and function have not been clarified in the adult CNS.One of the unique characteristics of periostin is its variable regions in the C-terminal regions, which contain exons 15 to 23 ( Figure 1A). The presence of splicing variants of periostin is becoming the center of the interest, given that various splicing...

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

“…At present, clinically important or well-known variants are as follows: POSTN 1, a full-length form containing 23 exons; POSTN 2, which lacks exon 17; POSTN 3, which lacks exon 21; and POSTN 4, which lacks exons 17 and 21 [34]. For example, POSTN 2 exhibited neuroprotective effects and accelerated neurite outgrowth in transient focal cerebral ischemia in mice associated with Akt phosphorylation [35]. On the other hand, in experimental SAH in mice, POSTN 1 caused BBB disruption and brain edema formation [13].…”

Increased concentration of serum periostin is associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage

“…The results showed that periostin 2, not periostin 1 was overexpressed at 24 hours after tMCAo. Exogenously injection of periostin 2 could reduce infarct volume, which indicated that periostin 2 exhibit anti‐hypoxia property and an protective effect . While on the contrary, previous study found that periostin was higher expressed in heart failure and inhibited expression of periostin could increase survival rate, which indicated that inhibition of periostin might be a potential theraphy for heart failure .…”

“…15 Periostin was observed in neurons and increased in astrocytes at 24 hours after transient middle cerebral artery occlusion (tMCAo), which indicated that periostin might play an important role in the pathologic process after stroke. 16 Recently, study showed that serum periostin concentrations in patients with traumatic brain injury (TBI) was significantly higher than healthy individuals and level of periostin was significantly associated with clinical severity. 17 While in SAH mouse model, periostin neutralization could alleviate EBI.…”

Oxidative Stress Does Not Predispose Neuronal Cells to Changes in G Protein Coupled (Opioid) Receptor Gene Expression in Cortical B50 Neurons in Culture

“…It has been shown that intracellular Ca 2+ levels were elevated during hypoxic exposure leading to irreversible cell injury while the inhibition of Ca 2+ currents by opioid receptor stimulation by DAMGO, DSLET and ICI-199441, may serve as a neuroprotective mechanism in preventing Ca 2+ overload (Andersen 2004;Bossy-Wetzel et al 2004;Shimamura et al 2012), and this could be the situation with the protection proffered by the µ-, δ-and κ-opioid agonists used in this study. This mechanism of cellular regulation may be utilised during normal cell functioning and in response to oxidative stress like hypoxia (Andersen 2004;Shimamura et al 2012).…”

“…This mechanism of cellular regulation may be utilised during normal cell functioning and in response to oxidative stress like hypoxia (Andersen 2004;Shimamura et al 2012). The δ-, µ-and κ-opioid receptors have many similarities such as seven transmembrane domains existing as 60% identical sequences and being coupled to G i/o proteins.…”