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BACKGROUND: Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor (VEGF) may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. Minocycline, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis. OBJECTIVE: To observe the influence of minocycline on VEGF, interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) expression in Wistar rats with focal cerebral ischemia/reperfusion injury, and to study the neuroprotection mechanism of minocycline against focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING: Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008. MATERIALS: A total of 36 female, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocycline treatment, and ischemia/reperfusion groups, with 12 rats in each group. Minocycline (Huishi Pharmaceutical Limited Company, China) was dissolved to 0.5 g/L in normal saline. METHODS: A 0.5-1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia/reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline (50 mg/kg) 12 and 24 hours following ischemia and reperfusion, whereas the other groups received saline at the corresponding time points. MAIN OUTCOME MEASURES: mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA. RESULTS: Minocycline decreased the focal infarct volume. VEGF, IL-1β, and TNF-αexpression was upregulated in the ischemia-perfusion group after injury. Following minocycline treatment, IL-1β and TNF-α expression was significantly downregulated, and VEGF was significantly upregulated, compared with the ischemia/reperfusion group (all P < 0.01). Expression of VEGF, IL-1β, and TNF-α was greater in the ischemia-perfusion and minocycline treatment groups, compared with sham-operated animals (P < 0.01). CONCLUSION: Minocycline can reduce expression of IL-1β and TNF-α, and increase VEGF expression, in the rat brain following cerebral ischemia/reperfusion. From these findings, a hypothesis can be formed that minocycline attenuates neuroinflammation and enhances recovery of vascular integrity during the process of cerebral ischemia/reperfusion.
BACKGROUND: Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor (VEGF) may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. Minocycline, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis. OBJECTIVE: To observe the influence of minocycline on VEGF, interleukin-1 beta necrosis factor alpha (TNF-α) expression in Wistar rats with focal cerebral ischemia / reperfusion injury, and to study the neuroprotection mechanism of minocycline against focal cerebral ischemia / reperfusion injury. DESIGN, TIME AND SETTING: Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008. MATERIALS: A total of 36 fema le, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocycline treatment, and ischemia / reperfusion groups, with 12 rats in each group. Minocycline (Huishi Pharmaceutical Limited Company, China ) was dissolved to 0.5 g / L in normal saline. METHODS: A 0.5-1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia / reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline mg / kg) MAIN OUTCOME MEASURES: mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA. RESULTS: Minocycline decreased the focal infa rctvolume of VEGF, IL-1β, and TNF-αexpression was upregulated in the ischemia-perfusion group after injury. Following minocycline treatment, IL-1β and TNF-α expression were significantly downregulated, and VEGF was significantly upregulated, compared with the ischemia / Expression of VEGF, IL-1β, and TNF-α was greater in the ischemia-perfusion and minocycline treatment groups, compared with sham-operated animals (P <0.01). CONCLUSION: Minocycline can reduce expression of IL-1β and TNF-α, and increase VEGF expression, in the rat brain following cerebral ischemia / reperfusion. From these findings, a hypothesis can be formed that minocycline attenuates neuroinflammation and enhances recovery of vascular integrity during the process of cerebral ischemia / reperfusion.