Microglial Hexokinase 2 Regulates Neuroinflammatory Responses Following Traumatic Brain Injury in mice

Claudia Mera-Reina, Juan F. Codocedo, Paul B. Fallen, Jack Scott, Cristian A. Lasagna-Reeves and Gary E. Landreth

Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA

TBI causes an immediate primary injury resulting from mechanical tissue damage. This is followed by a prolonged secondary injury phase characterized by neuroinflammation, cellular dysfunction, and progressive tissue damage that can contribute to long-term neurological impairment. Microglia are key mediators of this secondary inflammatory response and undergo metabolic adaptations that support inflammatory signaling. Hexokinase 2 (HK2), a glycolytic enzyme implicated in regulating microglial inflammatory activity, has emerged as a potential therapeutic target in neurological disease; however, its role following TBI remains poorly understood. We therefore investigated whether pharmacological and genetic inhibition of HK2 attenuates post-traumatic neuroinflammation and improves functional recovery after experimental TBI