Deletion of aquaporin-4 is neuroprotective during the acute stage of micro traumatic brain injury in mice

•Two-photon microscopy was use to examine the role of AQP4 in micro TBI.•AQP4 deletion reduced cells death, astrocytes swelling and lesion volume.•Treatment inhibiting AQP4 can be used to protect micro brain injury. Micro traumatic brain injury (TBI) is the most common type of brain injury, but the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet, which plays an important role in brain edema. However, little is known about the role of AQP4 in micro TBI. Here, we examined the role of AQP4 in the pathogenesis of micro TBI in a closed-skull brain injury model, using two-photon microscopy. Our results indicate that AQP4 deletion reduced cell death, water content, astrocyte swelling and lesion volume during the acute stage of micro TBI. Our data revealed that astrocyte swelling is a decisive pathophysiological factor in the acute phase of this form of micro brain injury. Thus, treatments that inhibit AQP4 could be used as a neuroprotective strategy for micro TBI.