Chronic Treatment With Minocycline Preserves Adult New Neurons and Reduces Functional Impairment After Focal Cerebral Ischemia
- 1 January 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 38 (1), 146-152
- https://doi.org/10.1161/01.str.0000251791.64910.cd
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemiaNeurobiology of Disease, 2006
- Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthoodNature Neuroscience, 2006
- Neurogenesis in Rats After Focal Cerebral Ischemia is Enhanced by IndomethacinStroke, 2005
- Adult Neurogenesis and the Ischemic ForebrainJournal of Cerebral Blood Flow & Metabolism, 2005
- Irradiation attenuates neurogenesis and exacerbates ischemia‐induced deficitsAnnals of Neurology, 2004
- Inflammatory Blockade Restores Adult Hippocampal NeurogenesisScience, 2003
- Inflammation is detrimental for neurogenesis in adult brainProceedings of the National Academy of Sciences of the United States of America, 2003
- Irradiation induces neural precursor-cell dysfunctionNature Medicine, 2002
- Neuronal replacement from endogenous precursors in the adult brain after strokeNature Medicine, 2002
- Correlation between changes in apparent diffusion coefficient and induction of heat shock protein, cell-specific injury marker expression, and protein synthesis reduction on diffusion-weighted magnetic resonance images after temporary focal cerebral ischemia in ratsJournal of Neurosurgery, 2002