Propofol Administration Modulates AQP-4 Expression and Brain Edema After Traumatic Brain Injury

摘要

The increased intracranial pressure caused by brain edema following traumatic brain injury (TBI) always leads to poor patient prognosis. Aquaporin-4 (AQP-4) plays an important role in edema formation and resolution, which may provide a novel therapeutic target for edema treatment. In this present study, we found that propofol treatment, within a short time, after TBI significantly reduced brain edema in a controlled cortical injury rat model and suppressed in vivo expression of AQP-4. The ameliorating effect of propofol was associated with attenuated expression of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). In addition, the regulatory effect of propofol on AQP-4 expression was investigated in cultured astrocytes. Results showed that propofol could block the stimulatory effect of IL-1beta and TNF-alpha on AQP-4 expression in cultured astrocytes. We also found that both NFkappaB and p38/MAPK pathways were involved in IL-1beta and TNF-alpha-induced AQP-4 expression and that propofol functions as a dual inhibitor of NFkappaB and p38/MAPK pathways. In conclusion, treatment with propofol, within a short time, after TBI attenuates cerebral edema and reduces the expression of AQP-4. Propofol modulates acute AQP-4 expression by attenuating IL-1beta and TNF-alpha expression and inhibiting IL-1beta and TNF-alpha induced AQP-4 expression.