软脑膜吻合术或软脑膜侧支动脉对于缺血性中风后恢复脑血流量（CBF）至关重要。血管平滑肌细胞（VSMC）被假设可以调节这种适应性反应的程度，而这一过程背后的具体分子机制仍在研究中。 SNHG12 是一种长链非编码 RNA，已被证明可以影响多种与血管生成相关的疾病，包括骨肉瘤和胃癌。然而，SNHG12 在侧支动脉生成相关中风期间收缩性 VSMC 去分化中的作用仍不清楚。在此，我们证明 SNHG12 是 MMP9 和 VSMC 去分化的正调节因子，可增强脑血管闭塞后软脑膜侧支动脉的生成。软脑膜侧支重塑受到 VSMC 中 SNHG12-MMP9 信号之间串扰的限制，该串扰是通过排斥性引导分子 a (RGMa) 调节介导的。因此，靶向 SNHG12 可能代表一种改善侧支功能、神经组织健康和缺血性中风后功能恢复的治疗策略。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Leptomeningeal anastomoses or pial collateral arteries are crucial for restoring cerebral blood flow (CBF) after an ischemic stroke. Vascular smooth muscle cells (VSMCs) are hypothesized to regulate the extent of this adaptive response, while the specific molecular mechanisms underlying this process are still being investigated. SNHG12, a long non-coding RNA, has been shown to influence several diseases related angiogenesis, including osteosarcoma and gastric cancer. However, the role of SNHG12 in contractile VSMC dedifferentiation during collateral arteriogenesis-related strokes remains unclear. Here we demonstrated that SNHG12 is a positive regulator of MMP9 and VSMC dedifferentiation, which enhances pial collateral arteriogenesis following cerebrovascular occlusion. Pial collateral remodeling is limited by the crosstalk between SNHG12-MMP9 signaling in VSMCs, which is mediated through repulsive guidance molecule a (RGMa) regulation. Thus, targeting SNHG12 may represent a therapeutic strategy for improving collateral function, neural tissue health, and functional recovery following ischemic stroke.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.