【Objective】 To investigate the time dependent manner of glutamate concentration in brain tissues of rodent model in different postnatal days and its intervention study. 【Methods】 Total 128 neonatal SD rats were divided into 4 groups according to postnatal days(P)∶P2, P6, P12, P18(n=32). Each group were randomly divided into 4 groups: hypoxic-ischemic brain damage(HIBD) group(H), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA) group(A), GYKI52466 group(G) and normal control group(N) (n=8). Standard HIBD models were set up according to Rice methods on rats of H, A, G groups. Rats of the A and G groups were injected drugs immediately after modeling. Brain tissue of all groups was collected to detect the glutamate concentration and observe the pathological changes. 【Results】 The results showed that there was a negative correlation between glutamate concentrations and postnatal ages (r=0.81, P<0.01). The glutamate concentration in brain tissues of P2 group was the maximum and was dramatically higher than those of P6 group, P12 group and P18 group, respectively[(670.2±139.4) μmol/gprot vs(576±139 )μmol/gprot,(670.2±139.4) μmol/gprot vs(441.9±114.9) μmol/gprot and(670.2±139.4) μmol/gprot vs(287.0±82.8) μmol/gprot, q=3.88,9.41,15.80,P<0.05 or 0.01]. The glutamate concentration in brain tissues of G group was the minimum and there were significant differences compared with those of A, H and N groups[(348.6±128.5) μmol/gprot vs(608.6±176.7) μmol/gprot, (348.6±128.5) μmol/gprot vs(554.2±206.2) μmol/gprot, (348.6±128.5) μmol/gprot vs(463.8±167.1) μmol/gprot, q=10.72,8.49,4.75,P<0.01]. Pathological changes were consistent with the changes of glutamate concentration in each group. 【Conclusions】 Glutamate concentration shows time dependent in brain tissue of different postnatal days represent to different developmental level of neonatal brain. There is a negative correlation between glutamate concentrations and postnatal days. Glutamate concentrations increase in HIBD cases and decrease with treatment of GYKI52466. Neuroprotective effect of GYKI52466 is more obvious in relative early stage of gestational age. Early intervention with GYKI52466 is expected to prevent and cure neonatal brain damage resulted from premature birth or asphyxia.
Key words
cerebral anoxia /
cerebral ischemia /
glutamate /
AMPA /
GYKI52466
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References
[1] Chidambaram SB, Muthiah R. Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics[J]. Int J Devl Neuroscience,2011,29:93-105.
[2] Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxici schemic brain damage in the rat[J]. Ann Neurol,1981,9:131-141.
[3] 安丽,孙若鹏,刘怡平,等.早期应用激活素A对新生大鼠缺氧缺血性脑损伤的预防作用[J].山东大学学报:医学版,2005,43(10):902-905.
[4] 张均田,张庆柱,张永祥.神经药理学[M].北京:人民卫生出版社,2008:73-77.
[5] Loría F, Petrosino S, Hernangómez M, et al. An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis[J]. Neurobiology of Disease,2010,37:166-176.
[6] Pingwei Z, Dmitri L, Mary EA, et al. Cannabinoid receptor activation reduces TNFa-Induced surface localization of AMPAR-type glutamate receptors and excitotoxicity[J]. Neuropharmacology,2010,58:551-558.
[7] Follet PL, Deng EB, Dai W, et al. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia:a protective role for topiramate[J]. J Neurosci,2004,24(18):4412-4420.
[8] Hagberg H, Bona E, Gilland E, et al. Hypoxic-ischemia model in the 7 day old rat: possibilities and short comings[J]. Acta Paediatr Suppl,1997,422:85-88.
[9] 杨锡强,易著文.儿科学[M].6版.北京:人民卫生出版社,2008:123-126.
[10] Gabor S, Miklos V, Geza S, et al. 2, 3-Benzodiazepine-type AMPA receptor antagonists and their neuroprotective effects[J]. J Neurochemistry,2008,52:166-183.
[11] Papazisis G, Pourzitaki C, Sardeli C, et al. Deferoxamine decreases the excitatory amino acid levels and improves the histological outcome in the hippocampus of neonatal rats after hypoxia-ischemia[J]. Pharmacological Research,2008,57:73-78.
[12] Suzanne MU, Mark PG. Hypoxic injury of isolated axons is independent of ionotropic glutamate receptors[J]. Neurobiology of Disease,2007,25:284-290.
[13] Mondal N, Bhat BV, Banupriya C, et al. Oxidative stress in perinatal asphyxia in relation to outcome[J]. Indian J Pediatr,2010,77(5):515-517.
[14] Dawn MB, Raymond CK, Lee JM. Rapid NMDA receptor phosphorylation and oxidative stress precede striatal neurodegeneration after hypoxic ischemia in newborn piglets and are attenuated with hypothermia[J]. Int J Devl Neuroscience,2008,26:67-76.
[15] Sahin S, Alkan T, Temel SG, et al. Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats[J]. J Clin Neuroscience,2010,17:227-231.
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