Zhvania Mzia G, Ksovreli Mariam, Japaridze Nadezhda J, Lordkipanidze Tamar G
Institute of Chemical Biology, Ilia State University, 3/5 K. Cholokhashvili Avenue, 0162 Tbilisi, Georgia; Department of Brain Ultrastructure and Nanoarchitecture, I. Beriitashvili Center of Experimental BioMedicine, 14, Gotua Street, 0160 Tbilisi, Georgia.
Institute of Chemical Biology, Ilia State University, 3/5 K. Cholokhashvili Avenue, 0162 Tbilisi, Georgia.
Micron. 2015 Jul;74:22-9. doi: 10.1016/j.micron.2015.03.015. Epub 2015 Apr 8.
A pentylenetetrazol (PTZ)-induced status epilepticus model in rats was used in the study. The brains were studied one month after treatment. Ultrastructural observations using electron microscopy performed on the neurons, glial cells, and synapses, in the hippocampal CA1 region of epileptic brains, demonstrated the following major changes over normal control brain tissue. (i) There is ultrastructural alterations in some neurons, glial cells and synapses in the hippocampal CA1 region. (ii) The destruction of cellular organelles and peripheral, partial or even total chromatolysis in some pyramidal cells and in interneurons are observed. Several astrocytes are proliferated or activated. Presynaptic terminals with granular vesicles and degenerated presynaptic profiles are rarely observed. (iii) The alterations observed are found to be dependent on the frequency of seizure activities following the PTZ treatment. It was observed that if seizure episodes are frequent and severe, the ultrastructure of hippocampal area is significantly changed. Interestingly, the ultrastructure of CA1 area is found to be only moderately altered if seizure episodes following the status epilepticus are rare and more superficial; (iv) alterations in mitochondria and dendrites are among the most common ultrastructural changes seen, suggesting cell stress and changes to cellular metabolism. These morphological changes, observed in brain neurons in status epilepticus, are a reflection of epileptic pathophysiology. Further studies at the chemical and molecular level of neurotransmitter release, such as at the level of porosomes (secretory portals) at the presynaptic membrane, will further reveal molecular details of these changes.
本研究采用大鼠戊四氮（PTZ）诱导的癫痫持续状态模型。在治疗一个月后对大脑进行研究。对癫痫大脑海马CA1区的神经元、胶质细胞和突触进行电子显微镜超微结构观察，结果显示与正常对照脑组织相比有以下主要变化。（i）海马CA1区的一些神经元、胶质细胞和突触存在超微结构改变。（ii）观察到一些锥体细胞和中间神经元的细胞器破坏以及周边、部分甚至完全的染色质溶解。多个星形胶质细胞增殖或活化。很少观察到带有颗粒小泡的突触前终末和退化的突触前轮廓。（iii）观察到的改变取决于PTZ治疗后癫痫发作活动的频率。据观察，如果癫痫发作频繁且严重，海马区的超微结构会发生显著变化。有趣的是，如果癫痫持续状态后的癫痫发作罕见且较表浅，CA1区的超微结构仅发生中度改变；（iv）线粒体和树突的改变是最常见的超微结构变化之一，提示细胞应激和细胞代谢改变。在癫痫持续状态的脑神经元中观察到的这些形态学变化反映了癫痫的病理生理学。在神经递质释放的化学和分子水平上进一步研究，例如在突触前膜的孔体（分泌门户）水平，将进一步揭示这些变化的分子细节。
