Magnolol Reduces Glutamate-Induced Neuronal Excitotoxicity and Protects against Permanent Focal Cerebral Ischemia Up to 4 Hours

作者：Lee Wei Ting^*; Lin Miao Hui; Lee E Jian; Hung Yu Chang; Tai Shih Huang; Chen Hung Yi; Chen Tsung Ying; Wu Tian Shung

来源：PLos One, 2012, 7(7): e39952.

DOI：10.1371/journal.pone.0039952

Neuroprotective efficacy of magnolol, 5,5%26apos;-dially-2,2%26apos;-dihydroxydiphenyl, was investigated in a model of stroke and cultured neurons exposed to glutamate-induced excitotoxicity. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Magnolol or vehicle was administered intraperitoneally, at 1 hr pre-insult or 1-6 hrs post-insult. Brain infarction was measured upon sacrifice. Relative to controls, animals pre-treated with magnolol (50-200 mg/kg) had significant infarct volume reductions by 30.9-37.8% and improved neurobehavioral outcomes (P%26lt;0.05, respectively). Delayed treatment with magnolol (100 mg/kg) also protected against ischemic brain damage and improved neurobehavioral scores, even when administered up to 4 hrs post-insult (P %26lt; 0.05, respectively). Additionally, magnolol (0.1 mu M) effectively attenuated the rises of intracellular Ca2+ levels, [Ca2+](i), in cultured neurons exposed to glutamate. Consequently, magnolol (0.1-1 mu M) significantly attenuated glutamate-induced cytotoxicity and cell swelling (P%26lt;0.05). Thus, magnolol offers neuroprotection against permanent focal cerebral ischemia with a therapeutic window of 4 hrs. This neuroprotection may be, partly, mediated by its ability to limit the glutamate-induced excitotoxicity.

• 出版日期2012-7-9
• 单位中国医科大学