Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia.
Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia.
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DOI：
10.1038/cddis.2010.33
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发表时间：
2010-07-15
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
锂被用于治疗双相情感障碍。据报道，锂对成人脑缺血模型具有神经保护作用。本研究的目的是评估锂在新生儿缺氧缺血性脑损伤模型中的作用。9日龄雄性大鼠单侧缺氧缺血（HI），损伤后立即腹腔注射2 mmol/kg氯化锂。每隔24小时注射1 mmol/kg锂。幼崽在HI后6、24或72小时被杀死。在HI后72小时，与对照组相比，锂使梗死体积从24.7±2.9减少到13.8±3.3 mm3(44.1%)，总组织损失（变性+缺乏生长）从67.4±4.4减少到38.4±5.9 mm3（43.1%）。皮质、海马、丘脑和纹状体损伤减轻。锂减少缺血诱导的糖原合成酶激酶3β和细胞外信号调节激酶的去磷酸化，calpain和caspase-3的激活，线粒体细胞色素c和凋亡诱导因子的释放，以及自噬。我们认为锂可能通过抑制神经元凋亡来减轻HI后的脑损伤。使用的锂剂量与双相情感障碍患者的剂量范围相同，这表明锂可以安全地用于避免新生儿脑损伤。
Lithium is used in the treatment of bipolar mood disorder. Reportedly, lithium can be neuroprotective in models of adult brain ischemia. The purpose of this study was to evaluate the effects of lithium in a model of neonatal hypoxic–ischemic brain injury. Nine-day-old male rats were subjected to unilateral hypoxia–ischemia (HI) and 2 mmol/kg lithium chloride was injected i.p. immediately after the insult. Additional lithium injections, 1 mmol/kg, were administered at 24-h intervals. Pups were killed 6, 24 or 72 h after HI. Lithium reduced the infarct volume from 24.7±2.9 to 13.8±3.3 mm3 (44.1%) and total tissue loss (degeneration + lack of growth) from 67.4±4.4 to 38.4±5.9 mm3 (43.1%) compared with vehicle at 72 h after HI. Injury was reduced in the cortex, hippocampus, thalamus and striatum. Lithium reduced the ischemia-induced dephosphorylation of glycogen synthase kinase-3β and extracellular signal-regulated kinase, the activation of calpain and caspase-3, the mitochondrial release of cytochrome c and apoptosis-inducing factor, as well as autophagy. We conclude that lithium could mitigate the brain injury after HI by inhibiting neuronal apoptosis. The lithium doses used were in the same range as those used in bipolar patients, suggesting that lithium might be safely used for the avoidance of neonatal brain injury.
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DOI：
10.1073/pnas.96.15.8745
发表时间：
1999-07-20
影响因子：
11.1
作者：
Chalecka-Franaszek, E;Chuang, DM
通讯作者：
Chuang, DM
锂通过抑制肌醇单磷酸酶诱导自噬。
影响因子：
7.8
作者：
Sarkar, Sovan;Floto, R Andres;Berger, Zdenek;Imarisio, Sara;Cordenier, Axelle;Pasco, Matthieu;Cook, Lynnette J;Rubinsztein, David C
通讯作者：
Rubinsztein, David C
DOI：
10.1523/jneurosci.5832-08.2009
发表时间：
2009-02-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wang X;Carlsson Y;Basso E;Zhu C;Rousset CI;Rasola A;Johansson BR;Blomgren K;Mallard C;Bernardi P;Forte MA;Hagberg H
通讯作者：
Hagberg H
影响因子：
3.4
作者：
Brywe, KG;Mallard, C;Hagberg, H
通讯作者：
Hagberg, H
影响因子：
6.1
作者：
Carloni, Silvia;Buonocore, Giuseppe;Balduini, Walter
通讯作者：
Balduini, Walter