Experimental Study On Preventive Effects Of Sodium Ferulate On Hyperoxia-Induced Seizures Via The Action Of Platelet-Derived Growth Factor-B Protein

Hyperoxia-induced seizures is the most severe and typical symptom of hyperbaric oxygen toxicity. The main features of hyperoxia-induced seizures are seizure attack, twitch , spasm, opitsthotonus, the temporal stop of respiration , which may threaten life when serious. There have been various hypothesis to the pathogenesis of hyperoxia-induced seizures, but the mechanism is not clarified yetf and there is no practical progress in preventing hyperoxia-induced seizures. Recently, in the studies of applying Chinese tradition medicine to prevent acute oxygen toxicity, we find that ferulic acid, the effective component of Angelica sinensis, can prolong convulsion latency significantly. The mechanism is worth exploring.Our researches have proved that Sodium Ferulate can induce the secretion of platelet-derived growth factor(PDGF-BB) in the vascular endotithal cell. Expressed widely in many different types of cells, PDGF-BB is a multiple-effective growth factor, and can stimulate mitosis and growth of mesenchymal connective tissue-forming cells. In the developing and mature central nervous system, PDGF and PDGF receptors are widely expressed and have neurotrophic effects. Some researches reported that PDGF-BB suppressed the convulsion of Epoleply Model Mouse EL, and the Author concluded that PDGF-BB could protect the hippocampus of mice. PDGF-BB also prolongs oxygen convulsion latency. Based on the a-bove researches, we hypothesis that the anti-convulsion effects of Sodium Ferulate is by its upregulation of the expression of PDGF-BB in neurons, therefore, we carry out the following study.(1) we investigate the effects of Sodium Ferulate on the expression level of PDGF-B protein in the central nervous system by immunohisto- chemistry staining, (2)the effect of Sodium Ferulate and PDGF on the survival rate of cultured hippocampal neurons and cortical neurons of rats in the condition of HBO is measured by MTT. (3)the growth-promoting ability of PDGF-BB on cultured hippocampal and cortical neurons is studied by nissel staining and computer graph auto-assay system.The main results are as follows.(1) After the continuous injection of Sodium Ferulate via intraperitionl for 10 days (40mg/kg), We observe the expression of PDGF-B protein in the rat cortex and hippocampus by ABC immunohistochemistry staining. The results show that Sodium Ferulate can upregulate the expression of PDGF-B protein in the rat cortex and hippocampus .(2) There is no obvious influence on the survival rate of the rat hippocampal neurons and cortical neurons exposed to 0. 5MPa hyperbaric air (the oxygen partial pressure is 20KPa) 5 the survival rate of neurons decreases when exposed to 0. 5Mpa hyperbaric oxy-gen(the oxygen partial pressure is 0. 5MPa) j the longer time exposure, the lower survival rate. PDGF-BB (30ng/ml) can prevent cell death and promote the survival of neurons.(3) PDGF-BB can promote the growth of hippocampal and cortical neurons in vitro, and has neurotrophic effect to neurons.