title: Changes in HIF-1α, VEGF, NGF and BDNF levels in cerebrospinal fluid and their relationship with cognitive impairment in patients with cerebral infarction.
abstract: This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Ke
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wdsjkx@163.com.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid*; D002544:Cerebral Infarction / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000134:cerebrospinal fluid*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C579455:BDNF protein, human; D020932:Nerve Growth Factor