Journal
NEURAL REGENERATION RESEARCH
Volume 15, Issue 1, Pages 78-85Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.264465
Keywords
astrocytes; hippocampal CA1 region; ilexonin A; microglia; middle cerebral artery occlusion; neural stem cell; neuroprotection; transient focal cerebral ischemia
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Funding
- Natural Science Foundation of Fujian Province of China [2014J01327]
- Program for New Century Excellent Talents in Colleges and Universities of Fujian Province of China
- NCETFJ [0704]
- Professorial Academic Development Foundation of Fujian Medical University of China [JS09014]
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Ilexonin A is a compound isolated from the root of Ilex pubescens, a traditional Chinese medicine. Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia. However, the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear. Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats. Ilexonin A (20, 40 or 80 mg/kg) was administered immediately after ischemia/reperfusion. The astrocyte marker glial fibrillary acidic protein, microglia marker Iba-1, neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay. Expression levels of tumor necrosis factor-alpha and interleukin 1 beta were determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue. Astrocytes were activated immediately in progressively increasing numbers from 1, 3, to 7 days post-ischemia/reperfusion. The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A. Microglial cells remained quiescent after ischemia/reperfusion, but became activated after treatment with ilexonin A. Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-alpha and interleukin 1 beta in the hippocampus post-ischemia/reperfusion. The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion, probably through regulating astrocytes and microglia activation, promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors.
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