...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Brain research >Salutary and deleterious effects of acidity on an indirect measure of metabolic rate and ATP concentrations in CNS cultures.
【24h】

Salutary and deleterious effects of acidity on an indirect measure of metabolic rate and ATP concentrations in CNS cultures.

机译：酸度对中枢神经系统培养物中代谢率和ATP浓度的间接度量的有益和有害影响。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Acidosis has traditionally been considered to mediate certain types of hypoxic-ischemic injury to the brain. However, the recent demonstration that moderate acidosis will reduce NMDA-mediated currents suggested that acidity could actually protect against types of ischemia and excitotoxicity, and in vitro studies now support this idea. Prompted by this, we have utilized the silicon microphysiometer, a recently-developed instrument that allows for indirect real-time measurement of metabolic rate by detecting proton efflux from small numbers of cultured cells, to determine whether acidity has protective effects upon cellular metabolism. Reducing extracellular pH from 7.4 to as low as 6.0 caused prompt, step-wise, and reversible inhibition of proton efflux rate in cortical and hippocampal cultures both normally and restricted to either glycolysis or oxidative metabolism. Approximately half of the inhibition was due to acidotic effects of NMDA-mediated currents, as demonstrated with NMDA receptor antagonists. Such an inhibition of this indirect metabolic measure could be associated with constant or increased ATP concentrations and represent a beneficial decrease in energy demands upon a neuron. Alternatively, an inhibition of proton efflux rate could be associated with ATP depletion and reflect impaired energy production. We observed a complex interplay between these opposing patterns. Reducing pH to 6.7 for 20 min caused significantly increased ATP concentrations, and prevented excitotoxin-induced ATP depletion. These effects of acidosis involved both NMDA-dependent and- independent actions. More severe (less than pH 6.7) acidosis did not cause ATP concentrations to rise, and if sustained for more than an hour caused a significant decline in ATP concentrations. Thus, despite the recent emphasis on the surprising neuroprotective potential of acidosis, a drop in pH is still likely to have complex and mixed consequences for brain tissue.
机译：传统上认为酸中毒可介导某些类型的大脑缺氧缺血性损伤。但是，最近的证据表明中度酸中毒会减少NMDA介导的电流，这表明酸度实际上可以防止局部缺血和兴奋性毒性，目前的体外研究支持这一观点。为此，我们利用了硅微生理仪（一种最新开发的仪器），该仪器可通过检测少量培养细胞的质子流出来间接实时测量代谢率，从而确定酸度是否对细胞代谢具有保护作用。将细胞外pH从7.4降低至6.0会导致皮层和海马培养物中质子外排率的迅速，逐步和可逆抑制，这通常是正常的，并且仅限于糖酵解或氧化代谢。如NMDA受体拮抗剂所证实的，大约一半的抑制作用是由于NMDA介导的电流的酸中毒作用。这种间接代谢措施的抑制作用可能与恒定或增加的ATP浓度有关，并且代表了神经元能量需求的有益降低。或者，质子外排率的抑制可能与ATP消耗有关，并反映了能量产生受损。我们观察到这些相对模式之间的复杂相互作用。在20分钟内将pH降低至6.7会导致ATP浓度显着增加，并防止了由兴奋毒素诱导的ATP消耗。酸中毒的这些影响涉及NMDA依赖性和非依赖性作用。严重的酸中毒（低于pH 6.7）不会导致ATP浓度升高，如果持续超过一个小时，则会导致ATP浓度显着下降。因此，尽管最近强调了酸中毒的令人惊讶的神经保护潜力，但pH下降仍可能对脑组织产生复杂和混合的后果。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号