Mechanism And Role Of Aquaporin 4 In Brain Edema Formation Resulting From Brain Explosive Injury

Craniocerebral explosive injury is an important thesis in the Military Medicine. Brain edema accounts for much of the morbidity and mortality associated with head trauma. Unfortunately, we are currently limited in our ability to treat edema, as many of our treatments are either ineffective or result in unacceptable side effects. The discovery of Aquaporins rises a new hope for treatment of brain edema. It doesn't allow for passage of carbamide, glycerol and other neutral small ions except for water. Aquaporin-4 (AQP4) is the most abundant water channel in the brain. It is primarily expressed in glial cells at the blood-brain and the brain-CSF interfaces. AQP4 may play a central role in keeping water homeostasis in the brain. AQP4 levels are up-regulated in animal models of trauma. They have thus been implicated in the formation of brain edema. Knockout mice, without the aquaporin gene, appear to have reduced brain edema compared to their wild type brethren in models of brain edema. Inhibition of AQP4 may be a new therapeutic way for reducing cerebral water accumulation after trauma. However, the role of AQP4 in brain edema after Craniocerebral explosive injury remain unclear. There is no other medcine that can inhibit its function at present because it is a mercury insensitive water channel. RNA interference (RNAi) is a new powerful tool for functional genomic investigations.In this paper we establish an animal model of brain explosive injury in rat at the beginning of study. Then investigate the mechanism and effect of AQP4 in brain edema formation after explosive injury. In vitro we transfected astrocytes with a short hairpin plasmid vector pGenesil that can specifically suppress AQP4 expression. In vivo we injected this plasmid into right lateral ventricles of rat. Then we test the effect of inhibition of AQP4 and its influece on brain edema formation resulting from brain explosive injury.Part I: Establishment of an animal model and study on the pathological changes following brain explosive injury in rat1. 150 mg and 80 mg TNT detonators were exploded at 5 cm distance after 1 cm...