División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Ciudad de México, México.
J Cereb Blood Flow Metab. 2019 May;39(5):808-821. doi: 10.1177/0271678X17733640. Epub 2017 Oct 19.
Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus (TIDM) patients who are under intensive insulin therapy increasing the risk for severe hypoglycemia (SH). The consequences of RH are not well understood and its repercussions on neuronal damage and cognitive function after a subsequent episode of SH have been poorly investigated. In the current study, we have addressed this question and observed that previous RH during seven consecutive days exacerbated oxidative damage and neuronal death induced by a subsequent episode of SH accompanied by a short period of coma, in the parietal cortex, the striatum and mainly in the hippocampus. These changes correlated with a severe decrease in reduced glutathione content (GSH), and a significant spatial and contextual memory deficit. Administration of the antioxidant, N-acetyl-L-cysteine, (NAC) reduced neuronal death and prevented cognitive impairment. These results demonstrate that previous RH enhances brain vulnerability to acute hypoglycemia and suggests that this effect is mediated by the decline in the antioxidant defense and oxidative damage. The present results highlight the importance of an adequate control of moderate hypoglycemic episodes in TIDM.
中度反复性低血糖（RH）在接受强化胰岛素治疗的 1 型糖尿病（TIDM）患者中很常见，这会增加严重低血糖（SH）的风险。RH 的后果尚不清楚，其对 SH 后续发作后神经元损伤和认知功能的影响也研究甚少。在本研究中，我们研究了这一问题，并观察到，在连续 7 天出现 RH 之后，会加剧由后续伴有短暂昏迷的 SH 引起的氧化损伤和神经元死亡，这种损伤主要发生在顶叶皮层、纹状体和海马体中。这些变化与还原型谷胱甘肽（GSH）含量的显著下降以及空间和情景记忆缺陷有关。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）的给药可减少神经元死亡并预防认知障碍。这些结果表明，先前的 RH 会增加大脑对急性低血糖的易感性，并表明这种作用是通过抗氧化防御和氧化损伤的下降来介导的。目前的结果强调了在 TIDM 中充分控制中度低血糖发作的重要性。
