Tetramethylpyrazine improving cerebral microcirculation in Alzheimer's Disease mice

Cerebrovascular dysfunction plays a crucial role in the development and progression of Alzheimer's Disease (AD). Tetramethylpyrazine, a bioactive alkaloid monomer derived from Chinese herbal medicine Chuanxiong (Ligusticum chuanxiong), has been demonstrated to improve tissue microcirculation. However, direct in vivo monitoring of cerebral microcirculation is still challenging due to the presence and thickness of the skull. In this study, we constructed a visualized mouse cranial window and utilized photoacoustic microscopy, laser speckle imaging, and Laser Doppler flowmetry to investigate the effect of Tetramethylpyrazine on cortical microvascular function in normal mice, AD mice, and Tetramethylpyrazine-treated AD mice. Our results revealed impaired cerebral microvascular perfusion in AD mice, including significant reductions in blood flow velocity, oxygen saturation, and metabolic rate of oxygen. Tetramethylpyrazine treatment improved cortical microvascular function in AD mice, with endothelium-derived microvascular signals playing a key role in microvascular rhythmic motion. These findings suggest that Tetramethylpyrazine has the ability to enhance cortical microcirculation in AD mice through multiple mechanisms, particularly through endothelial improvement. Tetramethylpyrazine may serve as a potential candidate drug for AD treatment, and photoacoustic microscopy holds promise in the clinical observation of cortical microcirculation in AD.