P188Contributes To Traumatic Brain Injury Induced Cerebral Edema And AQP1, AQP4Expression

Objective: To explore the effects of poloxamer188(P188) on brain edema aftertraumatic brain injury (TBI), and to investigate its mechanisms through aquaporinspathway.Methods: TBI model was established by weight drop device in adult mice based onpreviously reported procedures. Animals were grouped into sham, TBI only, P188treated,and saline vehicle groups. Animals were sacrificed at different time point posttrauma andbrains were removed, sagittally dissected and dried. Brain water content of separatehemispheres was calculated from the weight difference before and after drying andcalculated according to the Elliott formula. cerebral water content（CWC） was detectedfrom1h to168h post TBI to certify the peak time point of edema, and then dosage effectand injection time effect of P188were analyzed to confirm the suitable dose andadministrating time point for further investigation. P188（0.1ml,4mg/ml）or0.9%NaCl（0.1ml）was pretreated with a vena caudalis injection30min before TBI. Animals weresacrificed at1h,3h,6h,24h, and48h after suffering TBI. Injured brain samples wereobtained, and CWC were detected. The permeability of blood-brain barrier(BBB) wasdetected with labelled compound of evans blue(EB). The mRNA levels of cerebral edemarelated protein AQP1and AQP4were detected by RT-PCR, and western blot andimmunofluorescence for AQP4protein expression were also assessed.Results: Brain edema occurred6h, and peaked at24h after TBI in our TBI model.4mg/ml is the best efficient dose and a vena caudalis injection30min before or within1hafter TBI attenuated TBI induced brain edema. The permeability of BBB was resealedeffectually by P188. Up-regulation of AQP4mRNA and protein started in early time pointsafter TBI and then declined later. In contrast, P188pretreatment significantly suppressedTBI-induced activation of AQP4at24h and48h post-TBI（P＜0.05). AQP1do not beaffected obviously. AQP4were labeled with GFAP and Vwf, but not β-Tubulin. Conclusion: P188treatment could attenuat TBI-induced cerebral edema, restore BBBintegraty, and regulate AQP4expression. Our findings suggested that plasmelemma permi-bility should be a therapeutic target for TBI treatment.