Terahertz Photons Ameliorate Traumatic Brain Injury and Reduce Neuroinflammation via the Cyclic Adenosine Monophosphate Signaling Pathway

Traumatic brain injury (TBI) has the highest incidence among common neurological disorders and remains the leading cause of mortality and disability among all kinds of injuries, yet specific therapies for TBI are still unavailable. In the present study, we found that short-term administration of terahertz (THz) photons during the acute phase of TBI ameliorated brain damage and cognitive deficits. THz photons induced a reduced population of microglia and an increased number of anti-inflammatory phenotypes of microglia. In vivo and in vitro validation further revealed that THz photons inhibit inflammasome activation. Blocking adenylyl cyclase type 9 (AC9) in microglia attenuated the beneficial effects of THz irradiation, indicating that THz-irradiation-mediated inhibition of inflammasome activation involves the AC9/cyclic adenosine monophosphate/NLR and pyrin domain-containing protein 3 signaling pathway. Compared with drug therapy, THz photon technology offers noninvasiveness, accurate tissue targeting, and on-demand application and removal. In conclusion, this study established a THz-photon-based therapeutic paradigm, highlighting its potential as a therapy for TBI and potentially other forms of acute brain injury.