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- 刘正言主任医师 副教授
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医院：
复旦大学附属华山医院
科室：
神经外科
- Chronic Treatment With Minocycline Preserves Adult New Neurons and Reduces Functional Impairment After Focal
- 作者：刘正言|发布时间：2009-05-16|浏览量：1467次
Chronic Treatment With Minocycline Preserves Adult New
Neurons and Reduces Functional Impairment After Focal
Cerebral Ischemia
Zhengyan Liu, MD; Yang Fan, MS; Seok Joon Won, PhD; Melanie Neumann, PhD; Dezhi Hu, MD;
Liangfu Zhou, MD; Philip R. Weinstein, MD; Jiaing Liu, PhD上海华山医院神经外科刘正言
Background and Purpose?Evidence suggests that activated microglia are detrimental to the survival of new hippocampal
neurons, whereas blocking inflammation has been shown to restore hippocampal neurogenesis after cranial irradiation
and seizure. The aim of this current study is to determine the effect of minocycline on neurogenesis and functional
recovery after cerebral focal ischemia.
Methods?Four days after temporary middle cerebral artery occlusion, minocycline was administered intraperitoneally for
4 weeks. BrdU was given on days 4 to 7 after middle cerebral artery occlusion to track cell proliferation. The number
of remaining new neurons and activated microglia were quantified in the dentate gyrus. Infarct volume was measured
to assess the treatment effect of minocycline. Motor and cognitive functions were evaluated 6 weeks after middle
cerebral artery occlusion.
Results?Minocycline delivered 4 days after middle cerebral artery occlusion for 4 weeks did not result in reduction in
infarct size but significantly decreased the number of activated microglia in the dentate gyrus. Minocycline also
significantly increased the number of newborn neurons that coexpressing BrdU and NeuN without significantly
affecting progenitor cell proliferation in the dentate gyrus. Lastly, minocycline significantly improved motor
coordination on the rotor rod, reduced the preferential use of the unaffected limb during exploration, reduced the
frequency of footfalls in the affected limb when traversing on a horizontal ladder, and improved spatial learning and
memory in the water maze test.
Conclusions?Minocycline reduces functional impairment caused by cerebral focal ischemia. The improved function is
associated with enhanced neurogenesis and reduced microglia activation in the dentate gyrus and possibly improved
neural environment after chronic treatment with minocycline. (Stroke. 2007;38:146-152.)
Key Words: dentate gyrus hippocampus inflammation memory motor function
Neurons and Reduces Functional Impairment After Focal
Cerebral Ischemia
Zhengyan Liu, MD; Yang Fan, MS; Seok Joon Won, PhD; Melanie Neumann, PhD; Dezhi Hu, MD;
Liangfu Zhou, MD; Philip R. Weinstein, MD; Jiaing Liu, PhD上海华山医院神经外科刘正言
Background and Purpose?Evidence suggests that activated microglia are detrimental to the survival of new hippocampal
neurons, whereas blocking inflammation has been shown to restore hippocampal neurogenesis after cranial irradiation
and seizure. The aim of this current study is to determine the effect of minocycline on neurogenesis and functional
recovery after cerebral focal ischemia.
Methods?Four days after temporary middle cerebral artery occlusion, minocycline was administered intraperitoneally for
4 weeks. BrdU was given on days 4 to 7 after middle cerebral artery occlusion to track cell proliferation. The number
of remaining new neurons and activated microglia were quantified in the dentate gyrus. Infarct volume was measured
to assess the treatment effect of minocycline. Motor and cognitive functions were evaluated 6 weeks after middle
cerebral artery occlusion.
Results?Minocycline delivered 4 days after middle cerebral artery occlusion for 4 weeks did not result in reduction in
infarct size but significantly decreased the number of activated microglia in the dentate gyrus. Minocycline also
significantly increased the number of newborn neurons that coexpressing BrdU and NeuN without significantly
affecting progenitor cell proliferation in the dentate gyrus. Lastly, minocycline significantly improved motor
coordination on the rotor rod, reduced the preferential use of the unaffected limb during exploration, reduced the
frequency of footfalls in the affected limb when traversing on a horizontal ladder, and improved spatial learning and
memory in the water maze test.
Conclusions?Minocycline reduces functional impairment caused by cerebral focal ischemia. The improved function is
associated with enhanced neurogenesis and reduced microglia activation in the dentate gyrus and possibly improved
neural environment after chronic treatment with minocycline. (Stroke. 2007;38:146-152.)
Key Words: dentate gyrus hippocampus inflammation memory motor function
