Unlike hypoxia, hypoglycemia does not preferentially destroy GABAergic neurons in developing rat neocortex explants in culture

We tested whether hypoglycemia, like hypoxia, would preferentially destroy GABAergic nerve cells in the neocortex. To this end, rat neocortex explants dissected from 6-day-old rat pups and cultured up to a developmental stage approximately comparable to that of the newborn human neocortex, were exposed to hypoglycemia for different periods. Quantitative light microscopic and immunocytochemical evaluation of the cultures demonstrated that hypoglycemia does not preferentially destroy GABAergic but rather non-GABAergic neurons, a finding quite opposite to what was found after hypoxia. Recent biochemical data from other laboratories which seem to support this difference in neuronal vulnerability are discussed. It is concluded that perinatal hypoglycemia may not form such a serious threat with respect to the genesis of epilepsy as does hypoxia.     

丙丁酚对载脂蛋白E~(-/-)小鼠主动脉粥样硬化病变及病变处凝集素样氧化型低密度脂蛋白受体1表达的影响

目的观察丙丁酚对载脂蛋白E-/-小鼠主动脉粥样硬化斑块形成及主动脉凝集素样氧化型低密度脂蛋白受体1表达的影响,以探讨丙丁酚调节血脂以外的可能的抗动脉粥样硬化作用机制。方法将21只4周龄的雄性载脂蛋白E-/-小鼠随机分成基础饮食对照组、高脂饮食对照组和高脂饮食加丙丁酚组     

TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

低氧及运动致大鼠骨骼肌形态学改变的实验研究

目的观察低氧及低氧复合运动时,大鼠体重及腓肠肌显微、超微结构的变化,旨在探讨低氧状态下适当运动对骨骼肌的影响。方法建立大鼠低氧及低氧复合运动模型,运用光镜及透射电镜观察大鼠腓肠肌显微、超微结构的变化。结果低氧复合运动组较低氧安静组大鼠体重差异有显著性意义(P<0.05)。低氧复合运动组骨骼肌结构正常,线粒体数量增加,骨骼肌纤维增粗,毛细血管增生。结论低氧复合适当的运动能够维持骨骼肌的正常形态,增强骨骼肌的有氧代谢,起到保护骨骼肌的作用,从而提高骨骼肌的低氧适应能力,促进低氧习服。     

CT检查对新生儿缺氧缺血性脑病预后判断的价值

目的　探讨CT检查对判断新生儿缺氧缺血性脑病 (HIE)预后的价值。方法　对 85例HIE患儿分别在生后 1周内、2周～ 2个月、3～ 6个月、1～ 1 5岁进行CT检查 ;同时在生后12～ 14d进行新生儿行为神经测定 ;在 1～ 1 5岁测定发育商判断预后。结果　生后 1周内CT结果分度为重度者预后不良率为 4 0 9% (9/ 2 2 ) ,为中度者预后不良率为 5 7% (3/ 5 2 ) ;2个月时CT随访结果异常者预后不良率为 6 0 0 % (6 / 10 ) ;CT结果中度且 12～ 14d的NBNA评分≥ 35分与 <35分者的预后差异无显著性 ,CT结果重度且 12～ 14d的NBNA评分 <35分者有 72 7% (8/ 11)预后不良。结论　生后 1周内CT分度及生后 1个月左右随访结果 ,同时结合临床、生后 12～ 14dNBNA评分对判断HIE患儿的预后、制定治疗方案及疗程有重要意义。     

依托咪酯对大鼠皮层、海马脑片缺氧复氧损伤的保护作用

目的观察依托眯酯对大鼠皮层、海马脑片缺氧复氧损伤的保护作用及其机制。方法雄性SD大鼠10只,体重90-100 g,制备大脑皮质和海马脑片,随机分为对照组、缺氧复氧组、3 μmol ·L-1依托咪酯组、6μmol·L-1依托咪酯组、15 μmol·L-1依托咪酯组和6 μmol·L-1依托咪酯+γ-氨基丁酸 A(GABAA)受体拮抗剂Picrotoxin 50 μmol·L-1组。各组脑片缺氧10 min复氧120 min时,测定经三苯基氯化四唑氮染色的吸光度(A490),Fluo-3荧光染色后计算细胞内Ca2+浓度。结果缺氧复氧可导致大脑皮层、海马A490降低,细胞内Ca2+浓度升高,不同浓度依托咪酯可减弱缺氧复氧导致的上述改变,以 6 μmol·L-1依托咪酯的效果较好,且此作用可被GABAA受体拮抗剂完全拮抗。结论依托咪酯对大鼠皮层、海马脑片缺氧复氧损伤有一定的保护作用,可能通过GABAA受体介导,并降低Ca2+负荷有关。     

低氧对口腔鳞癌细胞系血管内皮生长因子和MMP-2的影响

目的 :研究低氧对体外培养的口腔鳞癌细胞系血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)和明胶酶 A(matrixmetalloproteinase 2 ,MMP 2 )的影响。 方法 :分别用酶联免疫吸附实验 (ELISA)和半定量逆转录聚合酶链反应 (RT PCR)测定了低氧处理不同时间段时口腔鳞癌细胞系TSCCa和GNM细胞的细胞中VEGF和MMP 2的活性和mRNA表达情况。结果 :低氧处理 4h时 ,VEGF和MMP 2的活性便显著增加 ,8h时达到最高 ,GNM细胞中VEGF和MMP 2分别增加 2倍和 2 .5倍 ;而TSCCa细胞中VEGF和MMP 2增加的更为明显 ,分别增加了 6倍和 4倍。RT PCR结果显示GNM细胞VEGF和MMP 2mRNA表达水平均较TSCCa细胞高 (P <0 .0 5 ) ,低氧处理时在TSCCa细胞中VEGF和MMP 2增加的尤为明显。结论 :低氧可通过调节口腔鳞癌细胞VEGF和MMP 2的活性和mRNA的表达在口腔鳞癌血管形成中起重要作用     

Neuroprotection by both NMDA and non-NMDA receptor antagonists in in vitro ischemia

We have investigated the relative contributions of oxygen and glucose deprivation to ischaemic neurodegeneration in organotypic hippocampal slice cultures. Cultures prepared from 10-day-old rats were maintained in vitro for 14 days and then deprived of either oxygen (hypoxia), glucose (hypoglycaemia), or both oxygen and glucose (ischaemia). Hypoxia alone induced degeneration selectively in CA1 pyramidal cells and this was greatly potentiated if glucose was removed from the medium. We have also characterised the effects of both pre-and post-treatment using glutamate receptor antagonists and the sodium channel blocker tetrodotoxin (TTX). Neuronal death following either hypoxia or ischaemia was prevented by pre-incubation with CNQX, MK-801 or tetrodotoxin. MK-801 or CNQX also prevented death induced by either hypoxia or ischaemia if added immediately post-insult, however, post-insult addition of TTX prevented hypoxic but not ischaemic damage. Organotypic hippocampal slice cultures are sensitive to both NMDA and non-NMDA glutamate receptor blockade and thus represent a useful in vitro system for the study of ischaemic neurodegeneration paralleling results reported using in vivo models of ischaemia.     

1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A₁ receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A₁ receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA₁ area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects.