Abstract:

Objective To explore the improvement in cognitive function after cerebral infarction based on the 2 ⁃（2 ⁃ chlorophenyl）quinazolin ⁃ 4 ⁃ yl dimethylcarbamate（2 ⁃ Cl ⁃ MGV ⁃ 1）/brain ⁃ derived neurotrophic factor （BDNF）⁃ tropomyosin receptor kinase B（TrkB）pathway. Methods Adult Sprague⁃Dawley rats were randomly divided into a control group，middle cerebral artery embolism（MCAO）group，and 2⁃Cl ⁃MGV ⁃1 group，20 in each group. Except the control group，other groups established MCAO models. 2⁃Cl⁃MGV⁃1 group was treated with 2⁃Cl⁃MGV⁃1 for 7 days after the model was established. The cerebral infarction area，spatial learning and memory impairment，mitochondrial damage and BDNF/TrkB signal pathway were assessed in each group. In vitro PC12 neuron cell lines were divided into the following three groups：control group（Con），oxygen and glucose deprivation/ reperfusion model（OGD/R）group，and 2⁃Cl⁃MGV⁃1 group. Except Con group，other groups established OGD/R models，and 2⁃Cl⁃MGV⁃1 group was treated with 25 μmol/L 2⁃Cl⁃MGV⁃1 for 24 hours. Cell viability was evaluated by CCK⁃8. Results As compared with MCAO group，the infarct area in 2⁃Cl⁃MGV⁃1 group decreased significantly （P < 0.05），and the number of Nissl bodies increased significantly（P < 0.05）. As compared with the control group，the escape latency was significantly increased in MCAO group（P < 0.001），while it was significantly shorter in 2⁃Cl ⁃MGV ⁃1 group than in MCAO group（P < 0.01）. On day 7，the number of crossing the platform in MCAO group was significantly lower than that in the control group（P < 0.001），while the number of crossing the platform in 2⁃Cl⁃MGV⁃1 group was significantly higher than that in MCAO group（P < 0.05）. As compared with the control group，cortical mitochondrial membrane potential and ATP production decreased significantly in MCAO group （P < 0.01），while increased markedly in 2⁃Cl⁃MGV⁃1 group（P < 0.05）. As compared with the control group，lev⁃ els of BDNF and TrkB protein in cerebral cortex neurons in MCAO group were significantly increased（P < 0.05）， and levels of BDNF and TrkB protein in 2⁃Cl⁃MGV⁃1 group were significantly higher than those in MCAO group （P < 0.05）. As compared with Con group，cell viability and ATP production decreased significantly in OGD/R group（P < 0.05），while increased significantly in 2⁃Cl⁃MGV⁃1 group（P < 0.05）. As compared with Con group， levels of BDNF and TrkB protein in OGD/R group increased significantly（P < 0.05），and levels of BDNF and TrkB protein in 2⁃Cl⁃MGV⁃1 group were significantly higher than those in MCAO group（P < 0.05）. Conclusions 2⁃Cl⁃MGV⁃1 can protect mitochondria from MCAO⁃induced cerebral ischemia/reperfusion injury and improve cogni⁃ tive function in rats. It may play a neuroprotective role by regulating BDNF/TrkB signaling pathway.

Key words:

2?Cl?MGV?1, brain?derived neurotrophic factor, tropomyosin receptor kinase B, mito? chondria, cognitive function