Long noncoding RNAs (lncRNAs) participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis. Homeobox A11 antisense RNA (HOXA11-AS) is a member of the lncRNA family that has been reported to participate in many inflammatory reactions; however, its role in traumatic brain injury remains unclear. In this study, we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling. The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats, increased brain edema and apoptosis, promoted the secretion of proinflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor α, and promoted the activation of astrocytes and microglia. Microglia were treated with 100 ng/mL lipopolysaccharide for 24 hours to establish in vitro cell models, and then transfected with pcDNA-HOXA11-AS, miR-124-3p mimic, or sh-MDK. The results revealed that HOXA11-AS inhibited miR-124-3p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation. Furthermore, lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes. Forced overexpression of miR-124-3p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes. However, the miR-124-3p-mediated anti-inflammatory effects were reversed by HOXA11-AS. These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the miR-124-3p-MDK axis. This study was approved by the Animal Protection and Use Committee of Southwest Medical University (approval No. SMU-2019-042) on February 4, 2019.

中文翻译：

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HOXA11-AS 加重外伤性脑损伤后小胶质细胞诱导的神经炎症

长链非编码 RNA (lncRNA) 通过介导神经炎症和细胞凋亡，参与创伤性脑损伤后的许多病理生理过程。Homeobox A11反义RNA（HOXA11-AS）是lncRNA家族的成员，据报道参与许多炎症反应；然而，其在创伤性脑损伤中的作用仍不清楚。在这项研究中，我们使用负重击打装置建立了大鼠创伤性脑损伤模型，并在建模前 2 周将 LV-HOXA11-AS 注射到右侧脑室。结果表明，HOXA11-AS的过表达加重了创伤性脑损伤大鼠的神经功能缺损，增加了脑水肿和细胞凋亡，促进了促炎因子interleukin-1β、interleukin-6和肿瘤坏死因子α的分泌，并促进星形胶质细胞和小胶质细胞的活化。用 100 ng/mL 脂多糖处理小胶质细胞 24 小时以建立体外细胞模型，然后用 pcDNA-HOXA11-AS、miR-124-3p 模拟物或 sh-MDK 转染。结果表明，HOXA11-AS 抑制 miR-124-3p 表达并促进 MDK 表达和 TLR4-核因子-κB 通路激活。此外，脂多糖增强了星形胶质细胞中有效的小胶质细胞诱导的炎症反应。miR-124-3p 的强制过表达或下调 MDK 抑制小胶质细胞活化和星形胶质细胞的炎症反应。然而，miR-124-3p 介导的抗炎作用被 HOXA11-AS 逆转。这些发现表明 HOXA11-AS 可以通过调节 miR-124-3p-MDK 轴来加重创伤性脑损伤后的神经炎症。本研究于2019年2月4日获得西南医科大学动物保护与利用委员会批准（批准号：SMU-2019-042）。