Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong Street, Taipei, 11221, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
J Transl Med. 2023 Aug 24;21(1):565. doi: 10.1186/s12967-023-04377-z.
Intracerebral hemorrhage (ICH) is a condition associated with high morbidity and mortality, and glia-mediated inflammation is a major contributor to neurological deficits. However, there is currently no proven effective treatment for clinical ICH. Recently, low-intensity pulsed ultrasound (LIPUS), a non-invasive method, has shown potential for neuroprotection in neurodegenerative diseases. This study aimed to investigate the neuroprotective effects and potential mechanisms of LIPUS on glia-mediated inflammation in ICH.
This study used 289 mice to investigate the effects of LIPUS on ICH. ICH was induced by injecting bacterial collagenase (type VII-S; 0.0375 U) into the striatum of the mice. LIPUS was applied noninvasively for 3 days, including a 2-h-delayed intervention to mimic clinical usage. The study evaluated neurological function, histology, brain water content, hemoglobin content, MRI, and protein expression of neurotrophic factors, inflammatory molecules, and apoptosis. In vitro studies investigated glia-mediated inflammation by adding thrombin (10 U/mL) or conditioned media to primary and cell line cultures. The PI3K inhibitor LY294002 was used to confirm the effects of PI3K/Akt signaling after LIPUS treatment.
LIPUS treatment improved neurological deficits and reduced tissue loss, edema, and neurodegeneration after ICH. The protective effects of LIPUS resulted from decreased glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling, which reduced cytokine expression and attenuated microglial activation-induced neuronal damage in vitro.
LIPUS treatment improved neurological outcomes and reduced glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling after ICH. LIPUS may provide a non-invasive potential management strategy for ICH.
脑出血（ICH）是一种与高发病率和高死亡率相关的疾病，胶质细胞介导的炎症是导致神经功能缺损的主要原因。然而，目前临床上还没有有效的治疗方法。最近，低强度脉冲超声（LIPUS）作为一种非侵入性方法，在神经退行性疾病中显示出了神经保护作用的潜力。本研究旨在探讨 LIPUS 对 ICH 中胶质细胞介导的炎症的神经保护作用及其潜在机制。
本研究使用 289 只小鼠来研究 LIPUS 对 ICH 的影响。ICH 通过向小鼠纹状体注射细菌胶原酶（VII-S 型；0.0375 U）来诱导。LIPUS 以非侵入性方式进行 3 天的治疗，包括 2 小时延迟干预以模拟临床应用。研究评估了神经功能、组织学、脑水含量、血红蛋白含量、MRI 和神经营养因子、炎症分子和细胞凋亡的蛋白表达。体外研究通过添加凝血酶（10 U/mL）或条件培养基到原代和细胞系培养物中来研究胶质细胞介导的炎症。PI3K 抑制剂 LY294002 用于确认 LIPUS 治疗后 PI3K/Akt 信号的作用。
LIPUS 治疗改善了 ICH 后的神经功能缺损，减少了组织损失、水肿和神经退行性变。LIPUS 的保护作用是通过抑制 PI3K/Akt-NF-κB 信号通路，减少细胞因子表达和减轻小胶质细胞激活诱导的神经元损伤来实现的。
ICH 后，LIPUS 通过抑制 PI3K/Akt-NF-κB 信号通路，改善了神经功能预后，减轻了胶质细胞介导的炎症。LIPUS 可能为 ICH 提供了一种非侵入性的潜在治疗策略。
