Comelli M C, Guidolin D, Seren M S, Zanoni R, Canella R, Rubini R, Manev H
Fidia Research Laboratories, Abano Terme, Italy.
Neuroscience. 1993 Jul;55(2):473-90. doi: 10.1016/0306-4522(93)90517-j.
A focal, unilateral thrombotic stroke was produced in the rat sensorimotor cortex. The time course of expression and localization of the immediate early inducible genes: c-fos, c-jun, zif268; nerve growth factor, brain-derived neurotrophic factor and the related tyrosine kinase high-affinity receptor (trkB) messenger RNAs were studied by in situ hybridization. The levels of messenger RNAs for c-fos, zif268, brain-derived neurotrophic factor (but not nerve growth factor) and trkB were consistently increased in cortex ipsilaterally to the lesion, while c-jun messenger RNA content was only slightly increased. The brain-derived neurotrophic factor messenger RNA was increased from 2 to 18 h following the stroke, mainly in cells having a normal morphological appearance. The trkB messenger RNA displayed temporal and spatial increases similar to brain-derived neurotrophic factor messenger RNA. The time course and pattern of expression of immediate early inducible gene and trophic factor messenger RNAs did not clearly support a causal relationship between these two families of factors. The observed messenger RNA increases were greatly attenuated by the non-competitive N-methyl-D-aspartate-sensitive glutamate receptor antagonist (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine , but substantially unaffected by the non-N-methyl-D-aspartate receptor antagonist 2,3-dihydroxy-6-nitrosulphanoylbenzoquinoxaline. The results suggest a major contribution of N-methyl-D-aspartate-sensitive glutamate receptor activation to the transcriptionally directed events subsequent to stroke. Future studies should clarify the contribution of these processes to either the progression of neuronal degeneration or the establishment of protective compensatory responses.
在大鼠感觉运动皮层诱发局灶性单侧血栓性中风。通过原位杂交研究即刻早期诱导基因：c-fos、c-jun、zif268；神经生长因子、脑源性神经营养因子及相关酪氨酸激酶高亲和力受体（trkB）信使核糖核酸的表达时间进程和定位。在损伤同侧的皮层中，c-fos、zif268、脑源性神经营养因子（而非神经生长因子）和trkB的信使核糖核酸水平持续升高，而c-jun信使核糖核酸含量仅略有增加。脑源性神经营养因子信使核糖核酸在中风后2至18小时增加，主要在形态正常的细胞中。trkB信使核糖核酸的增加在时间和空间上与脑源性神经营养因子信使核糖核酸相似。即刻早期诱导基因和神经营养因子信使核糖核酸的表达时间进程和模式并不明确支持这两类因子之间存在因果关系。观察到的信使核糖核酸增加被非竞争性N-甲基-D-天冬氨酸敏感型谷氨酸受体拮抗剂（+）-5-甲基-10,11-二羟基-5H-二苯并（a,d）环庚烯-5,10-亚胺显著减弱，但基本不受非N-甲基-D-天冬氨酸受体拮抗剂2,3-二羟基-6-亚硝基磺酰基苯并喹喔啉的影响。结果表明，N-甲基-D-天冬氨酸敏感型谷氨酸受体激活对中风后转录导向事件有主要作用。未来的研究应阐明这些过程对神经元变性进展或保护性代偿反应建立的作用。
