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...
