Tsuiki K, Takada A, Nagahiro S, Grdisa M, Diksic M, Pappius H M
Cone Laboratory for Neurosurgical Research, Montreal Neurological Institute and Hospital, Quebec, Canada.
J Neurochem. 1995 Mar;64(3):1319-25. doi: 10.1046/j.1471-4159.1995.64031319.x.
Previous studies have demonstrated that focal freezing lesions in rats cause a widespread decrease of cortical glucose use in the lesioned hemisphere and this was interpreted as a reflection of depression of cortical activity. The serotonergic neurotransmitter system was implicated in these alterations when it was shown that (1) cortical serotonin metabolism was increased widely in focally injured brain and (2) inhibition of serotonin synthesis prevented the development of cortical hypometabolism. In the present studies we applied an autoradiographic method that uses the accumulation of the 14C-labeled analogue of serotonin alpha-methylserotonin to assess changes in the rate of serotonin synthesis in injured brain. The results confirmed that 3 days after the lesion was made, at the time of greatest depression of glucose use, serotonin synthesis was significantly increased in cortical areas throughout the injured hemisphere. The increase was also seen in the dorsal hippocampus and area CA3, as well as in the medial geniculate and dorsal raphe, but not in any other subcortical structures including median raphe. Present results suggest that the functional changes in the cortex of the lesioned hemisphere are associated with an increased rate of serotonin synthesis mediated by activation of the dorsal raphe. We also documented by alpha-[14C]aminoisobutyric acid autoradiography that there was increased permeability of the blood-brain barrier, but this was restricted to the rim of the lesion.
先前的研究表明，大鼠的局灶性冷冻损伤会导致损伤半球皮质葡萄糖利用广泛减少，这被解释为皮质活动抑制的反映。当发现（1）局灶性损伤的大脑中皮质5-羟色胺代谢广泛增加，以及（2）抑制5-羟色胺合成可阻止皮质代谢减退的发展时，5-羟色胺能神经递质系统与这些改变有关。在本研究中，我们应用了一种放射自显影方法，该方法利用5-羟色胺α-甲基5-羟色胺的14C标记类似物的积累来评估损伤大脑中5-羟色胺合成速率的变化。结果证实，损伤后3天，在葡萄糖利用最受抑制时，整个损伤半球的皮质区域5-羟色胺合成显著增加。在背侧海马和CA3区以及内侧膝状体和背侧中缝核也观察到了增加，但在包括中缝核在内的任何其他皮质下结构中均未观察到。目前的结果表明，损伤半球皮质的功能变化与背侧中缝核激活介导的5-羟色胺合成速率增加有关。我们还通过α-[14C]氨基异丁酸放射自显影记录到血脑屏障通透性增加，但这仅限于损伤边缘。
