Gallyas Ferenc, Csordás Attila, Schwarcz Attila, Mázló Mária
Department of Neurosurgery, Faculty of Medicine, Pécs University, Rét utca 2, 7623 Pécs, Hungary.
Exp Brain Res. 2005 Jan;160(4):473-86. doi: 10.1007/s00221-004-2037-4. Epub 2004 Oct 9.
"Dark" neurons were produced in the cortex of the rat brain by hypoglycemic convulsions. In the somatodendritic domain of each affected neuron, the ultrastructural elements, except for disturbed mitochondria, were remarkably preserved during the acute stage, but the distances between them were reduced dramatically (ultrastructural compaction). Following a 1-min convulsion period, only a few neurons were involved and their environment appeared undamaged. In contrast, 1-h convulsions affected many neurons and caused swelling of astrocytic processes and neuronal dendrites (excitotoxic neuropil). A proportion of "dark" neurons recovered the normal structure in 2 days. The non-recovering "dark" neurons were removed from the brain cortex through two entirely different pathways. In the case of 1-h convulsions, their organelles swelled, then disintegrated and finally dispersed into the neuropil through large gaps in the plasma membrane (necrotic-like removal). Following a 1-min convulsion period, the non-recovering "dark" neurons fell apart into membrane-bound fragments that retained the compacted interior even after being engulfed by astrocytes or microglial cells (apoptotic-like removal). Consequently, in contrast to what is generally accepted, the "dark" neurons produced by 1-min hypoglycemic convulsions do not die as a consequence of necrosis. As regards the case of 1-h convulsions, it is assumed that a necrotic-like removal process is imposed, by an excitotoxic environment, on "dark" neurons that previously died through a non-necrotic pathway. Apoptotic neurons were produced in the hippocampal dentate gyrus by intraventricularly administered colchicine. After the biochemical processes had been completed and the chromatin condensation in the nucleus had reached an advanced phase, the ultrastructural elements in the somatodendritic cytoplasm of the affected cells became compacted. If present in an apparently undamaged environment such apoptotic neurons were removed from the dentate gyrus through the apoptotic sequence of morphological changes, whereas those present in an impaired environment were removed through a necrotic-like sequence of morphological changes. This suggests that the removal pathway may depend on the environment and not on the death pathway, as also assumed in the case of the "dark" neurons produced by hypoglycemic convulsions.
低血糖惊厥可在大鼠大脑皮质产生“暗”神经元。在每个受影响神经元的体树突区域，除线粒体紊乱外，超微结构元件在急性期显著保存，但它们之间的距离大幅减小（超微结构致密化）。惊厥1分钟后，仅有少数神经元受累，其周围环境未受损。相比之下，惊厥1小时会影响许多神经元，并导致星形胶质细胞突起和神经元树突肿胀（兴奋性毒性神经毡）。一部分“暗”神经元在2天内恢复正常结构。未恢复的“暗”神经元通过两种完全不同的途径从大脑皮质中清除。在惊厥1小时的情况下，它们的细胞器肿胀，然后解体，最终通过质膜上的大间隙分散到神经毡中（类坏死清除）。惊厥1分钟后，未恢复的“暗”神经元解体为膜结合碎片，即使被星形胶质细胞或小胶质细胞吞噬后，其内部仍保持致密（类凋亡清除）。因此，与普遍观点相反，由1分钟低血糖惊厥产生的“暗”神经元并非因坏死而死亡。至于惊厥1小时的情况，据推测，兴奋性毒性环境会对先前通过非坏死途径死亡的“暗”神经元施加类坏死清除过程。脑室注射秋水仙碱可在海马齿状回产生凋亡神经元。生化过程完成且细胞核内染色质凝聚达到晚期后，受影响细胞的体树突细胞质中的超微结构元件变得致密。如果这些凋亡神经元存在于明显未受损的环境中，它们会通过凋亡形态变化序列从齿状回中清除，而存在于受损环境中的则通过类坏死形态变化序列清除。这表明清除途径可能取决于环境而非死亡途径，低血糖惊厥产生的“暗”神经元情况也是如此。
