Chronic cerebral hypoperfusion can cause learning and memory impairment and neuronal damage resembling the effects observed in vascular dementia. PPAR-gamma agonists were shown to modulate inflammatory response and neuronal death following cerebral ischemia. The present study was designed to evaluate possible neuroprotective effects of rosiglitazone, a PPAR-gamma agonist, in rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent bilateral occlusion of the common carotid arteries. Oral administration of rosiglitazone (1.5, 3, and 6 mg/kg/day) or vehicle was carried out for 5 weeks, starting one week before the surgery. Cognitive performance was assessed using the Morris water maze. The density of S100B protein-immunoreactive astrocytes and the OX-42-labeled microglial activation were estimated. Synaptogenesis was also evaluated by the measurement of synaptophysin, the pre-synaptic vesicular protein, level via western blotting technique. Cerebral hypoperfusion for 30 days induced a significant cognitive impairment along with hyperactivation of both microglial and astroglial cells, and reduction of synaptophysin level. Rosiglitazone treatment (3 and 6 mg/kg) not only suppressed the activation of astrocytes and microglia markedly but also alleviated the impairment of memory and increased the synaptophysin level. In conclusion, our results suggest that the chronic administration of rosiglitazone significantly prevents chronic cerebral hypoperfusion-induced brain damage, at least, partly through suppressing glial activation and preserving synaptic plasticity. Thus, it appears that rosiglitazone may be a promising pharmacological agent in the development of therapeutic approaches for the prevention or treatment of cerebrovascular diseases.
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Chao, Xiaodong
Zhou, Jun
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Urumqi Gen Hosp PLA, Dept Pharm, Urumqi 830000, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Zhou, Jun
Chen, Tao
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Chen, Tao
Liu, Wenbo
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Liu, Wenbo
Dong, Wenpeng
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Fourth Mil Med Univ, Inst Digest Dis, Xi Jing Hosp, Xian 710032, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Dong, Wenpeng
Qu, Yan
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Qu, Yan
Jiang, Xiaofan
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Jiang, Xiaofan
Ji, Xituan
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Ji, Xituan
Zhen, Haining
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Zhen, Haining
Fei, Zhou
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Chao, Xiaodong
Zhou, Jun
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h-index: 0
机构:
Urumqi Gen Hosp PLA, Dept Pharm, Urumqi 830000, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Zhou, Jun
Chen, Tao
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h-index: 0
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Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Chen, Tao
Liu, Wenbo
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h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Liu, Wenbo
Dong, Wenpeng
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Inst Digest Dis, Xi Jing Hosp, Xian 710032, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Dong, Wenpeng
Qu, Yan
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h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Qu, Yan
Jiang, Xiaofan
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h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Jiang, Xiaofan
Ji, Xituan
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h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Ji, Xituan
Zhen, Haining
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China
Zhen, Haining
Fei, Zhou
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R ChinaFourth Mil Med Univ, Dept Neurosurg, Xi Jing Inst Clin Neurosci, Xi Jing Hosp, Xian 710032, Shannxi, Peoples R China