Luhmann H J, Mudrick-Donnon L A, Mittmann T, Heinemann U
Institute of Neurophysiology, University of Köln, Germany.
Eur J Neurosci. 1995 Feb 1;7(2):180-91. doi: 10.1111/j.1460-9568.1995.tb01054.x.
The long-term structural and functional consequences of transient forebrain ischaemia were studied with morphological, immunohistochemical and in vitro electrophysiological techniques in the primary somatosensory cortex of Wistar rats. After survival times of 10-17 months postischaemia, neocortical slices obtained from ischaemic animals were characterized by a pronounced neuronal hyperexcitability in comparison with untreated age-matched controls. Extra- and intracellular recordings in supragranular layers revealed all-or-none long-latency recurrent responses to orthodromic synaptic stimulation of the afferent pathway. These responses were characterized by durations up to 1.7 s, by multiple components and by repetitive synaptic burst discharges. The reversible blockade of this late activity by DL-amino-phosphonovaleric acid (APV) suggested that this activity was mediated by N-methyl-D-aspartate (NMDA) receptors. The peak conductance of inhibitory postsynaptic potentials was significantly smaller in neurons recorded in neocortical slices obtained from ischaemic animals than those from the controls. However, the average number of parvalbumin (PV)-labelled neurons per mm3, indicative of a subpopulation of GABAergic interneurons, and the average number and length of dendritic processes arising from PV-containing cells was not significantly different between ischaemic and control cortex. The prominent dysfunction of the inhibitory system in ischaemic animals occurred without obvious structural alterations in PV-labelled cells, indicating that this subpopulation of GABAergic interneurons is not principally affected by ischaemia. Our data suggest a long-term down-regulation of inhibitory function and a concurrent NMDA receptor-mediated hyperexcitability in ischaemic neocortex. These alterations may result from structural and/or functional properties of inhibitory non-PV-positive neurons or permanent functional modifications on the subcellular molecular level, i.e. alterations in the phosphorylation status of GABA and/or NMDA receptors. The net result of these long-term changes is an imbalance between the excitatory and inhibitory systems in the ischaemic cortex with the subsequent expression and manifestation of intracortical hyperexcitability.
运用形态学、免疫组织化学和体外电生理技术，在Wistar大鼠的初级体感皮层中研究了短暂性前脑缺血的长期结构和功能后果。在缺血后10 - 17个月的存活期后，与未处理的年龄匹配对照组相比，从缺血动物获得的新皮层切片的特点是神经元明显过度兴奋。颗粒上层的细胞外和细胞内记录显示，对传入通路的正向突触刺激有全或无的长潜伏期复发反应。这些反应的特点是持续时间长达1.7秒、有多个成分以及重复性突触爆发放电。DL-氨基膦酸戊酸（APV）对这种晚期活动的可逆性阻断表明，这种活动是由N-甲基-D-天冬氨酸（NMDA）受体介导的。在从缺血动物获得的新皮层切片中记录的神经元中，抑制性突触后电位的峰值电导明显小于对照组的神经元。然而，每立方毫米中帕瓦丁（PV）标记神经元的平均数，这是GABA能中间神经元亚群的指标，以及含PV细胞产生的树突过程的平均数和长度，在缺血皮层和对照皮层之间没有显著差异。缺血动物中抑制系统的明显功能障碍在PV标记细胞中没有明显的结构改变，这表明GABA能中间神经元的这个亚群主要不受缺血影响。我们的数据表明，缺血新皮层中抑制功能长期下调，同时存在NMDA受体介导的过度兴奋。这些改变可能源于抑制性非PV阳性神经元的结构和/或功能特性，或亚细胞分子水平上的永久性功能修饰，即GABA和/或NMDA受体磷酸化状态的改变。这些长期变化的最终结果是缺血皮层中兴奋和抑制系统之间的失衡，随后出现皮层内过度兴奋的表现。
