Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice
Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice
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小鼠长期多种微生物败血症期间高血糖的神经病理学相关性
DOI：
10.1097/shk.0000000000000403
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发表时间：
2015
期刊：
影响因子：
3.1
通讯作者：
I. Vanhorebeek
中科院分区：
文献类型：
--
作者：
R. Sonneville;I. Derese;M. Marques;L. Langouche;S. Derde;L. Châtre;F. Chrétien;D. Annane;T. Sharshar;G. Van den Berghe;I. Vanhorebeek
摘要葡萄糖中毒可能在引起危重病的神经系统并发症中起着至关重要的作用。我们研究了在高血糖下观察到的致命性人类危重病的神经病理学改变是否存在，并且可以通过在盲肠结扎和穿刺诱导的长时间脓毒症小鼠模型中维持正常血糖来减弱。将小鼠随机分为中度高血糖组（>8.3 mmol/L，n = 8）和正常血糖组（4.4-6.7 mmol/L，n = 8）。5天后，将脓毒症小鼠的海马和额叶皮质与健康对照小鼠的海马和额叶皮质进行比较（n = 8）。高血糖危重病小鼠血糖为7.8 ± 1.3 mmol/L，血糖正常危重病小鼠血糖为6.1 ± 0.7 mmol/L（P = 0.007）。高血糖病鼠额叶皮层（P = 0.01）和海马（P = 0.06）神经元损伤率是健康鼠的2倍。额叶皮层神经元损伤在正常脑电刺激下明显减轻（P = 0.04）。无论血糖控制如何，危重病患者海马区星形胶质细胞密度和激活状态降低了4倍（P <0.02），但额叶皮层没有降低。在高血糖重症小鼠的两个脑区中，小胶质细胞的数量是正常小鼠的2倍至4倍（P <0.002），但仅在额叶皮质中，它们的数量减少（P = 0.0008）。仅高血糖病小鼠额叶皮质凋亡细胞密度和羰基化蛋白丰度显著高于正常对照组（P = 0.05）。在长期多微生物败血症的小鼠模型中，显著的神经病理学变化发展为神经元损伤、受损的星形胶质细胞活化、增加的小胶质细胞、细胞凋亡和羰基化蛋白的积累。当用胰岛素预防高血糖时，这些变化被部分预防或减弱。额叶皮质比海马更容易受到高血糖的伤害。
ABSTRACT Glucose toxicity may play a crucial role in evoking neurologic complications of critical illness. We studied whether the neuropathological alterations in fatal human critical illness observed under hyperglycemia are present and can be attenuated by maintaining normoglycemia in a mouse model of prolonged sepsis induced by cecal ligation and puncture. Mice were randomized to moderate hyperglycemia (>8.3 mmol/L, n = 8) or normoglycemia (4.4–6.7 mmol/L, n = 8). After 5 days, hippocampus and frontal cortex from septic mice were compared with those from healthy controls (n = 8). Blood glucose was 7.8 ± 1.3 mmol/L in hyperglycemic and 6.1 ± 0.7 mmol/L in normoglycemic critically ill mice (P = 0.007). The percentage of damaged neurons was twofold higher in frontal cortex (P = 0.01) and hippocampus (P = 0.06) of hyperglycemic ill mice than that of healthy mice. In frontal cortex, neuronal damage was attenuated under normoglycemia (P = 0.04). Critical illness reduced astrocyte density and activation status fourfold in hippocampus (P ⩽ 0.02), but not in frontal cortex, irrespective of glycemic control. Microglia were twofold to fourfold more abundant in both brain areas of hyperglycemic critically ill mice (P ⩽ 0.002), but only in frontal cortex were they reduced in number with normoglycemia (P = 0.0008). The density of apoptotic cells and abundance of carbonylated proteins were significantly higher than normal in frontal cortex of hyperglycemic ill mice only (P = 0.05). In a mouse model of prolonged polymicrobial sepsis, remarkable neuropathological changes develop with neuronal damage, impaired astrocyte activation, increased microglia, apoptosis, and accumulation of carbonylated proteins. These changes were partially prevented or attenuated when hyperglycemia was prevented with insulin. Frontal cortex appeared more vulnerable to hyperglycemic insults than hippocampus.
影响因子：
15.9
作者：
Suh, Sang Won;Gum, Elizabeth T.;Swanson, Raymond A.
通讯作者：
Swanson, Raymond A.