Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri, USA.
Diabetes. 2010 Apr;59(4):1055-62. doi: 10.2337/db09-1495. Epub 2010 Jan 19.
Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia.
Nine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurrent moderate (25-40 mg/dl) hypoglycemia (RH) or saline injections. On the fourth day, rats were subjected to a hyperinsulinemic (0.2 units x kg(-1) x min(-1)) severe hypoglycemic ( approximately 11 mg/dl) clamp for 60 or 90 min. Neuronal damage was subsequently assessed by hematoxylin-eosin and Fluoro-Jade B staining. The functional significance of severe hypoglycemia-induced brain damage was evaluated by motor and cognitive testing.
Severe hypoglycemia induced brain damage and striking deficits in spatial learning and memory. Rats subjected to recurrent moderate hypoglycemia had 62-74% less brain cell death and were protected from most of these cognitive disturbances.
Antecedent recurrent moderate hypoglycemia preconditioned the brain and markedly limited both the extent of severe hypoglycemia-induced neuronal damage and associated cognitive impairment. In conclusion, changes brought about by recurrent moderate hypoglycemia can be viewed, paradoxically, as providing a beneficial adaptive response in that there is mitigation against severe hypoglycemia-induced brain damage and cognitive dysfunction.
尽管胰岛素治疗实现的强化血糖控制会增加中度和重度低血糖的发生率，但由于重度低血糖导致认知障碍的临床报告差异很大。有人假设，反复发生的中度低血糖会使大脑产生适应，并防止严重低血糖引起的损伤。
9 周龄雄性 Sprague-Dawley 大鼠接受连续 3 天的反复中度（25-40mg/dl）低血糖（RH）或生理盐水注射。第四天，大鼠接受 60 或 90 分钟高胰岛素（0.2 单位 x kg(-1) x min(-1)）严重低血糖（约 11mg/dl）钳夹。随后通过苏木精-伊红和 Fluoro-Jade B 染色评估神经元损伤。通过运动和认知测试评估严重低血糖引起的脑损伤的功能意义。
严重低血糖导致脑损伤和明显的空间学习和记忆障碍。反复发生中度低血糖的大鼠脑内细胞死亡减少 62-74%，并且大部分认知障碍得到保护。
先前反复发生的中度低血糖使大脑产生适应，显著限制了严重低血糖引起的神经元损伤和相关认知障碍的程度。总之，反复发生的中度低血糖引起的变化可以被视为提供了一种有益的适应性反应，因为它减轻了严重低血糖引起的脑损伤和认知功能障碍。
