Long-term hypothermia amplified neuroprotection by antagonizing intracranial pressure rebound after severe traumatic brain injury in rats

Long-term hypothermia has been reported to prevent intracranial pressure (ICP) rebound in clinical patients, but the duration for hypothermia and the corresponding ICP data are not available. This study investigated the optimal duration of long-term hypothermia in traumatic brain injury (TBI) rats, and observed the effect on ICP and neurological function. In this study, we established a rat severe TBI model with electronic Controlled Cortical Injury device, and implemented hypothermia (33 °C) for different durations. The motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test, brain water content was calculated by the wet-dry weight method, Evan's blue staining was used to measure the blood-brain barrier (BBB) permeability, the change of hippocampal neurons was observed by Nissl staining, the expressions of BrdU, NeuN, and CD86 positive cells were detected by immunofluorescence staining, and the expressions of Bcl-2, Bax, iNOS, IL-10, and Arg-1 were detected by Western blot. We found that therapeutic hypothermia improved neurological recovery after TBI with declining ICP, reducing brain edema, decreasing BBB permeability, promoting neurogenesis, inhibiting apoptosis, and regulating inflammation. Moreover, 48 h hypothermia amplified the neuroprotective effect after injury on the basis of 4 or 24 h hypothermic treatment. Both 4 and 24 h hypothermia led to ICP rebound during or after rewarming, whereas 48 h hypothermia completely abolished ICP rebound. Our study suggests that long-term hypothermia amplifies neuroprotection after TBI by antagonizing ICP rebound.