Neuroinflammation and blood-brain barrier disruption in Japanese encephalitis virus infection: mechanisms, therapeutic targets, and intervention strategies.

Japanese encephalitis virus (JEV), as a neurotropic flavivirus, remains a primary cause of viral encephalitis and poses a significant public health challenge. Its pathogenic mechanism centers on the pathological interaction between blood-brain barrier (BBB) disruption and uncontrolled neuroinflammation, which collectively promote JEV neuroinvasion and result in irreversible brain damage. Therefore, elucidating the molecular mechanisms by which JEV disrupts the BBB and induces neuroinflammation is crucial for developing novel therapeutic strategies. This paper systematically elucidates the mechanisms by which JEV induces BBB disruption and neuroinflammation, focusing on key viral and host factors. Furthermore, we summarize recent advances in innate immune responses during JEV infection and explore potential therapeutic strategies to alleviate neuroinflammation and restore BBB integrity. Finally, we explored key knowledge gaps, translational medicine challenges, and future research directions. Given the current lack of specific antiviral treatments, there is an urgent need to develop novel intervention approaches to improve clinical outcomes.