Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.

BACKGROUND

Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.

METHODS

In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.

RESULTS

After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.

CONCLUSIONS

These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.