MLC901, a Traditional Chinese Medicine protects the brain against global ischemia

被引:75
|
作者
Quintard, H. [1 ,2 ]
Borsotto, M. [1 ]
Veyssiere, J. [1 ]
Gandin, C. [1 ]
Labbal, F. [1 ]
Widmann, C. [1 ]
Lazdunski, M. [1 ]
Heurteaux, C. [1 ]
机构
[1] Univ Nice Sophia Antipolis, CNRS, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France
[2] Ctr Hosp Univ Nice Hop, Hop St Roch, F-06000 Nice, France
关键词
Global ischemia; NeuroAid; Neurogenesis; Akt; BDNF; Recovery; CEREBRAL-ISCHEMIA; STROKE RECOVERY; NEURONAL SURVIVAL; NEUROAID EFFICACY; MILD HYPOTHERMIA; CARDIAC-ARREST; DAMAGE; RESUSCITATION; NEUROGENESIS; CELL;
D O I
10.1016/j.neuropharm.2011.05.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Global ischemia leads to damage in the hippocampal CA1 region and is associated with behavioral deficits. NeuroAid (MLC601 and MLC901), a Traditional Chinese Medicine is used in China for patients after stroke. We have investigated here the effects of MLC901 on brain injury and deficits after global ischemia in the rat. Global ischemia induced by four-vessel occlusion resulted in degeneration of CM neurons. MLC901 (0.074 mg/ml) prevented both necrosis and apoptosis of neurons up to 3 h after ischemia. These positive MLC901 effects were associated with a decrease in Bax expression and in levels of the lipid peroxidation product malondialdehyde. Using the PI3-kinase inhibitor LY294002 we also demonstrated the critical role of the Akt pathway in MLC901-mediated neuroprotection. MLC901 enhanced neurogenesis. Furthermore, MLC901 improved functional recovery of rats after global ischemia as assessed by the Morris water maze. In this test MLC901 reduced the increase in escape latency and in swim distance induced by ischemia. MLC901 also improved post-ischemic grip strength. If observations made with rats can be extended to humans, then MLC901 will represent a novel therapeutic strategy after cardiac arrest with a clinically interesting time window of protection. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:622 / 631
页数:10
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