Abstract: Despite growing treatments for traumatic brain injury, there is still no ideal strategy for efficiently mitigating these processes. Ultrashort wave therapy, a type of physical factor therapy, has been widely used in various clinical treatments. However, its effects on traumatic brain injury and the underlying mechanisms are not well understood. In this study, we demonstrate that ultrashort wave treatment can significantly promote injury repair and alleviate emotional and cognitive disorders. Our data showed that ultrashort wave reduced the levels of pro-inflammatory factors and inhibited neuroinflammation. In vitro experiments showed that ultrashort wave inhibited activation of C8-D1A astrocytes and BV2 microglia. Furthermore, traumatic brain injury induced the expression of Piezo1, while ultrashort wave effectively suppressed this high expression. Administration of Yoda1, a Piezo1 agonist, to traumatic brain injury mice reversed the beneficial effects of ultrashort wave. Consistently, Yoda1 also reversed the inhibitory effect of ultrashort wave on activation of C8-D1A astrocytes. These findings indicate that ultrashort wave is an ideal therapeutic strategy for traumatic brain injury, which works by inhibiting Piezo1, reducing neuroinflammation, and promoting nerve repair after traumatic brain injury. 

Key words: astrocyte, cognitive disorders, emotional disorders, lesion repair, neuroinflammation, neurological disorders, Piezo1, traumatic brain injury, ultrashort wave