The Study On The Mechanism Of Diazepam To Protect Brain Radiation Injury

ObjectiveThe radiation injury is one of the serious complications in the radiation therapy. The research selects diazepam, a benzodiazepine receptor active agent, to protect the brain radiation injury. The experiments in vivo, tissue and protein level investigate the protective action of diazepam under the acute brain radiation injury in the early stage.MethodsA model of whole brain radiation injury in wakefulness was established in the Sprague-Dawley rat with the single dose of4 Mev electron beam. "Thermoplastics materials fixing cage" was created to keep rat awaking while brain radiation in order to eliminate the side effects from the anesthesia agents. The exactness and reliablility of the animal model was verified by observation of the changes in body weight, the examination of the head skin inside the field, and the nerve behavior grade point after radiation exposure.Three level irradiation dosages were selected: 30 Gy, 15 Gy and 2 Gy. Experiment animals were divided into such groups with the randomly, group 1: diazepam 5 mg/kg was given intraperitoneally 30 minutes before radiation; group 2: diazepam5 mg/kg was given intraperitoneally 15 minutes after radiation;group 3: irradiation with non-medicine used; group 4: diazepam5 mg/kg was given intraperitoneally before sham irradiation. Theobservation was done before radiation and 6 hours, 1 day, 1 week,1 month after irradiation.1 The effect of diazepam on the blood brain barrier (BBB) after irradiated:(1) In vivo: Magnetic resonance imaging(MRI) with the T1-Weighted images, T2-Weighted images and Gd-DTPA induced MRI enhancement images was used to find out the effects of diazepam on the brain tissue signal intensity and the enhancement rate at the each observed point.(2)Tissue level: Examining the content of the Evan's blue (EB) inside brain tissue was used to analysis the effect of diazepam on the BBB permeability quantitatively.(3)Protein level: Immunohistochemical staining was used to analysis the effect of diazepam on the expression of vascular endothelial growth factor (VEGF) in the brain tissue.2 The effect of diazepam on the nerve cell in the hippocampus region after irradiated: Observed to the changes of the pathomorphology with the Hematoxylin-eosin (HE) staining, and the effect of diazepam to the changes of influence degree.3 The effect of diazepam to the free radical after irradiated: Detected the effect of diazepam to the vigor of the superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) after the brain tissue homogenate.Results1 The rat awake cerebral radiation model was excellent withexact radiation field and dosage and good replication.2 Compare to the group irradiated with no-medicine used, diazepam had some protective action to the BBB, and could lighten the brain edema from the result of MRI, and also decreased BBB permeability from the result of EB examine. In addition, immunohistochemical staining confirmed that diazepam could be used decrease VEGF expression after irradiated.3 Diazepam could lighten the nerve cell's injury in the hippocampus region after irradiated.4 Diazepam could increase the vigor of SOD, and reduce the MDA contents after irradiated.5 The protective effect of pre-inject diazepam was better than the effect of post-inject.ConclusionDiazepam had protection action in some degree to the brain radiation injury and had a better effect with pre-injection in our observation.