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目的 探讨和厚朴酚对脑出血（intracerebral hemorrhage，ICH）小鼠神经损伤和认知功能的影响及其作用机制。 方法 将C57BL/6J小鼠随机分为假手术组，模型组，和厚朴酚低、中、高剂量组，以及和厚朴酚+抑制剂组。除假手术组外，其余组小鼠均通过自体血注入右侧基底神经节构建ICH模型。于ICH前15 min和ICH后1 h，和厚朴酚低、中、高剂量组分别腹腔注射10 mg/kg、20 mg/kg、40 mg/kg和厚朴酚，和厚朴酚+抑制剂组腹腔注射40 mg/kg和厚朴酚与5 μg/kg脑源性神经营养因子（brain derived neurotrophic factor，BDNF）-酪氨酸激酶受体B（tyrosine kinase receptor B，TrkB）-环磷酸腺苷反应元件结合蛋白（cyclic adenosine monophosphate response element binding protein，CREB）信号通路抑制剂K252a，假手术组、模型组腹腔注射等量的二甲基亚砜和生理盐水。采用改良的神经功能缺损评分（modified neurological severity score，mNSS）评估小鼠神经功能；通过Morris水迷宫实验计算逃避潜伏期、跨越原平台次数、目标象限停留时间百分比3个指标用于评估小鼠空间学习和记忆能力；苏木精-伊红（hematoxylin-eosin，HE）染色观察海马神经元病理学改变；原位末端转移酶标记（terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling，TUNEL）染色检测海马神经元凋亡率；酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测血清BDNF、TrkB水平；免疫印迹法检测海马组织BDNF、TrkB、CREB、磷酸化CREB（phosphorylated CREB，p-CREB）蛋白表达情况。 结果 与假手术组小鼠相比，模型组小鼠mNSS、海马神经元凋亡率升高，逃避潜伏期延长，跨越原平台次数减少，目标象限停留时间百分比降低，血清BDNF、TrkB及海马组织BDNF、TrkB、p-CREB/CREB水平降低（均P

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Phenytoin is one of the most well-known antiepileptic drugs that cause cognitive impairment which is closely related to cAMP response element-binding protein (CREB) brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor, has a documented role in neurogenesis and neuronal survival and cognitive impairment. Therefore, this study aimed to investigate the influence of powerful antioxidants: α-Toc and CoQ10 alone or combined in the preservation of brain tissues and the maintenance of memory formation in phenytoin-induced cognitive impairment in rats. The following behavioral test novel object recognition and elevated plus maze were assessed after 14 days of treatment. Moreover, VEGF, BDNF, TrkB, and CREB gene expression levels in the hippocampus and prefrontal cortex were estimated using RT-PCR. Both α-Toc and CoQ10 alone or combined with phenytoin showed improvement in behavioral tests compared to phenytoin. Mechanistically, α-Toc and/or CoQ10 decreases the VEGF mRNA expression, while increases BDNF-TrKB-CREB mRNA levels in hippocampus and cortex of phenytoin-treated rats. Collectively, α-Toc and/or CoQ10 alleviated the phenytoin-induced cognitive impairment through suppressing oxidative damage. The underlying molecular mechanism of the treating compounds is related to the VEGF and enhancing BDNF-TrkB-CREB signaling pathway. Our study indicated the usefulness α-Toc or CoQ10 as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress. [ABSTRACT FROM AUTHOR]