Ogata T, Nakamura Y, Tsuji K, Shibata T, Kataoka K
Department of Physiology, Ehime University, School of Medicine, Japan.
Neuroscience. 1993 Jul;55(2):445-9. doi: 10.1016/0306-4522(93)90513-f.
The effects of steroid hormones on glutamate neurotoxicity were examined in cultured spinal cord neurons. The extent of neuronal damage, produced by glutamate exposure for 15 min, was estimated based on the activity of lactate dehydrogenase released from degenerated neurons to the media during 24 h of post-exposure incubation. This damage was dependent on the glutamate concentrations used. The addition of dexamethasone, a synthetic steroid, in post-exposure media remarkably reduced the extent of damage in a dose-dependent manner. The half effective concentration for the steroid was approximately 0.7 microM, which was in the range of pharmacological concentration. Dexamethasone was effective even when it was added 2 h after glutamate exposure. Some endogenous steroid hormones--aldosterone, progesterone and testosterone--also showed similar neuroprotective effects. However, cholesterol, a precursor of these steroid hormones, had no effect on glutamate neurotoxicity. This direct protective effect on neurons against glutamate neurotoxicity may explain, at least partly, the mechanisms of beneficial effects of steroid hormones on in vivo spinal cord injury.
在培养的脊髓神经元中研究了类固醇激素对谷氨酸神经毒性的影响。基于暴露后24小时内从退化神经元释放到培养基中的乳酸脱氢酶活性，估计了谷氨酸暴露15分钟所产生的神经元损伤程度。这种损伤取决于所用的谷氨酸浓度。在暴露后培养基中添加合成类固醇地塞米松，以剂量依赖的方式显著降低了损伤程度。该类固醇的半数有效浓度约为0.7微摩尔，处于药理浓度范围内。即使在谷氨酸暴露2小时后添加地塞米松也有效。一些内源性类固醇激素——醛固酮、孕酮和睾酮——也显示出类似的神经保护作用。然而，这些类固醇激素的前体胆固醇对谷氨酸神经毒性没有影响。这种对神经元对抗谷氨酸神经毒性的直接保护作用可能至少部分解释了类固醇激素对体内脊髓损伤有益作用的机制。
