低強度超音波作為酸敏感離子通道一型對膠淋巴系統功能的調節因子

Abstract

超音波長期以來已廣泛應用於診斷與治療領域。近年來，低強度超音波（low-intensity ultrasound, LIUS）逐漸成為腦部研究中一種非侵入性的神經調控策略。越來越多的研究證據顯示，LIUS 可作為治療腦部疾病的非侵入性神經調控方法；其能以機械力精準作用於腦組織，同時避免造成不可逆的組織損傷與熱效應累積。 膠淋巴系統（glymphatic system）是大腦的清除途徑，負責腦脊髓液（cerebrospinal fluid, CSF）與腦間質液（interstitial fluid, ISF）之間的交換，以及代謝廢物的清除。而此過程高度依賴水通道蛋白四型（aquaporin-4, AQP4）的功能。膠淋巴系統功能受損已被認為與多種神經系統疾病的發生相關。 本研究探討酸敏感離子通道一型（Acid-Sensing Ion Channel 1a, ASIC1a）在膠淋巴系統功能中的角色，以及其是否可受到 LIUS 調控。研究中使用 ASIC1a 基因剔除（knockout, KO）小鼠與野生型（wild-type, WT）小鼠，並在有或無 LIUS 刺激的條件下，進行以螢光示蹤劑為基礎的腦脊髓液流動分析。 研究結果顯示，ASIC1a 會透過降低 AQP4 所介導的液體運輸而調節膠淋巴系統功能（初步可見趨勢為抑制）；相對地，LIUS 能夠對抗此抑制趨勢，並促進膠淋巴清除功能。這些結果指出，LIUS 可能作為一種調控 ASIC1a 介導之膠淋巴功能障礙的潛在工具，為與腦部清除功能受損相關的神經系統疾病提供一項具前景的治療策略。

Ultrasound has been in diagnostic and therapeutic use for a long while. In recent focus, low-intensity ultrasound (LIUS) has come into the non-invasive neuromodulation strategy in brain research. Growing evidence indicates that LIUS has emerged as a non-invasive neuromodulation approach to treating brain disorders. It has the ability to target brain tissue with mechanical force without causing irreversible damage and thermal accumulation. The glymphatic system is the brain’s clearance pathway responsible for cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange and metabolic waste removal, where aquaporin-4 (AQP4) channels are a major factor of the mechanism. Glymphatic function dysfunction is critical in culmination of neurological disorders. This study seeks to identify how Acid-Sensing Ion Channel 1a (ASIC1a) impact on glymphatic system function and its modulation by LIUS. ASIC1a knockout (KO) and wild-type (WT) mice are subjected to fluorescent tracer–based CSF flow analysis with or without LIUS stimulation. Our results demonstrate that ASIC1a is involved in modulating glymphatic function, with an inhibitory tendency, by reducing AQP4-mediated fluid transport. On the other hand, LIUS alleviates this inhibitory tendency and promotes glymphatic clearance. These findings establish LIUS as a potential modulator of ASIC1a in glymphatic dysfunction, offering a promising therapeutic strategy for neurological disorders associated with impaired brain clearance.