Study On The Role Of Excitatory Amino Acids In Development Of Acute Intoxicated Encephalopathy Induced By 1, 2-dichloroethane

[Objective] To explore the role of excitatory amino acid in acute intoxicated encephalopathy induced by l,2-dichloroethane(l,2-DCE) and provide a scientific basis for expounding the pathogenesis. [Methods] Sprague-Dawley rats were exposed to 1,2-DCE by continual static inhalation.Then ,the water content of brain tissues was measured by wet-dry method.Blood-brain barrier (BBB) permeability was detected with lanthanum nitrate.The content of glutamate (Glu), aspartate (Asp), glycine (Gly) and gamma-aminobutyric (GABA) in brain tissues was respectively determined by high performance liquid chromatography (HPLC) with fluorimetric detector.The expression of N-methyl-D-aspartate receptor-1 (NMDAR1), neuronal nitric oxide synthase (nNOS),immediately early gene c-fos and anti-apoptosis gene bcl-2 were observed by immunohistochemistry.Cell apoptosis was examined by Terminal deoxynucleotidyltransferase mediated dUTP-biotinnick-end-labeling(TUNEL). [ Results ] 1 . BBB breakdown was evident primarily at 5.0 g/m3 group. 2. Compared with that of control group, the water content of low and moderate dose groups had a significant elevation in cerebral cortex. The cerebral cortex water content of groups of various after-exposure duration was statistically higher than that of control groupand immediate-sacrificed group respectively. The medulla water content merely increased at 6h. 3. The content of Asp,Glu and Gly was more than control group,and that of Glu showed indifference between 10.0 g/m and 20.0 g/m3 group.Contrast to that of immediate-sacrificed group, groups of various after-exposure duration content of Asp increased, Glu increased at 4h and decended at 6h, Gly decreased at 6h.GABA showed indifference among groups. 4. NMDAR1 stain nurons mainly distributed at cerebral cortex and hippocampus, nNOS only expressed in brainstem and cerebellum. Fos protein was localized at nucleus of astrocytes of cerebral contex and hippocampus. The location of Bcl-2 protein was the same as nNOS. 5. Compared with that of control group, the percentage of positive cells of NMDAR1 and nNOS increased evidently at low and moderate dose groups. The percentage of both of groups of various after-exposure duration was statistically higher than that of control group and immediate-sacrificed group respectively.and there is difference between 4h and 6h groups.c-fos gene began to express at 30min and reach peak level at 1h.The expression of Bcl-2 gene didn't decrease until 6h group after exposure. 6. No cell apoptosis was seen in brain tissues. [ Conclusions ] The results showed that 1. EAA contributed to enhance secondary deleterious effects by overactivation of NMDAR1. 2. NO might afford neuroprotective effects during the pathogenesis. 3. The type of acute intoxicated brain edema induced by 1,2-DCE firstly was vasogenic brain edema. 4. The cell apoptosis was not seen in acute intoxicated encephalopathy induced by 1,2-DCE, which probably is the protective result of bcl-2.