Boris-Möller F, Kamme F, Wieloch T
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University Hospital, S-22185, Lund, Sweden.
Brain Res Mol Brain Res. 1998 Dec 10;63(1):163-73. doi: 10.1016/s0169-328x(98)00286-1.
The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.
采用原位杂交技术,研究了在大鼠海马中,经持续15分钟的常温(37℃)和保护性低温(33℃)短暂性脑缺血后,神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养素3(NT3)及神经营养素受体TrkB的mRNA表达情况。在耐受性较强的齿状回中,常温缺血在恢复约8小时时短暂诱导NGF mRNA表达,而NT3 mRNA水平在至少24小时的恢复期内降低。BDNF和TrkB水平短暂且显著升高,在恢复24小时时表达量最高。缺血期间低温降低了NGF mRNA的诱导,而BDNF mRNA表达的增加在恢复早期出现,缺血后NT3 mRNA的降低未受影响。此外,TrkB mRNA的表达增强,且与BDNF mRNA的升高同时出现。相比之下,CA3和CA1区域的神经营养素和TrkB mRNA没有变化。常温缺血后24小时BDNF mRNA的表达,因缺血期间低温而减弱。我们得出结论,保护性低温不会增加缺血敏感海马亚区中NGF、BDNF、NT3或TrkB mRNA的表达。相反,低温会诱导耐受性较强的齿状回中神经营养素mRNA发生改变,这可能为敏感区域提供保护。