Nagy A K, Houser C R, Delgado-Escueta A V
California Comprehensive Epilepsy Program, Southwest Regional Epilepsy Center, Veterans Administration Medical Center, Wadsworth Division, Los Angeles, CA 90073.
Brain Res. 1990 Oct 8;529(1-2):192-201. doi: 10.1016/0006-8993(90)90827-x.
Intact nerve endings (synaptosomes) have been isolated from spiking and non-spiking temporal cortex and hippocampus samples from 14 patients immediately after temporal lobectomy for intractable epilepsy. Synaptosomes were also prepared from frozen brain samples of humans with no known neurological diseases. Four adenosine triphosphatase (ATP)-metabolizing enzymes (ecto-ATPase, ecto-adenylate kinase, Na+,K(+)-ATPase and Ca2+,Mg2(+)-ATPase) were assayed in the synaptosomal fractions from the most spiking temporal cortex area (including focus) as well as from various regions of the hippocampus, and compared with enzyme activities of the least spiking or non-spiking temporal cortex of the same patient. Enzyme activities of the epileptic brain samples were also compared with values measured in the corresponding regions of normal brains. Ecto-ATPase activities of epileptic temporal cortex were decreased (approximately 30%) in both comparisons. In contrast to these findings, a substantially increased (in some cases 300%) ecto-ATPase activity was observed in the posterior part of epileptic hippocampus. We suggest that the higher than normal ecto-ATPase activity in this particular hippocampal region is related to the presence of granule cells and their efferent (or afferent) synaptic connections. The synaptosomal ecto-adenylate kinase showed alterations opposite to the changes found for the ecto-ATPase. The intrasynaptosomal ATPase (Na+,K(+)- and Ca2+,Mg2(+)-) were decreased in the epileptic hippocampus-, but not in the temporal cortex samples, in relation to the corresponding normal enzyme activity values. These complex alterations in synaptosomal ATP-metabolizing enzyme activities may be important elements of seizure development and maintenance in human temporal lobe epilepsy.
从14例因顽固性癫痫接受颞叶切除术的患者的颞叶皮质和海马样本中,在手术刚结束后立即分离出完整的神经末梢(突触体),这些样本来自发作期和非发作期的颞叶皮质和海马。突触体也从无已知神经疾病的人类冷冻脑样本中制备。在发作最频繁的颞叶皮质区域(包括病灶)以及海马的各个区域的突触体组分中检测了四种三磷酸腺苷(ATP)代谢酶(胞外ATP酶、胞外腺苷酸激酶、钠钾ATP酶和钙镁ATP酶),并与同一患者发作最少或不发作的颞叶皮质的酶活性进行比较。癫痫脑样本的酶活性也与正常脑相应区域测得的值进行比较。在两项比较中,癫痫颞叶皮质的胞外ATP酶活性均降低(约30%)。与这些发现相反,在癫痫海马后部观察到胞外ATP酶活性大幅增加(在某些情况下增加300%)。我们认为,这个特定海马区域中高于正常的胞外ATP酶活性与颗粒细胞及其传出(或传入)突触连接的存在有关。突触体胞外腺苷酸激酶的变化与胞外ATP酶的变化相反。与相应的正常酶活性值相比,癫痫海马中的突触体内ATP酶(钠钾ATP酶和钙镁ATP酶)活性降低,但在颞叶皮质样本中未降低。突触体ATP代谢酶活性的这些复杂变化可能是人类颞叶癫痫发作发展和维持的重要因素。