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Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD.
Behav Brain Res 2018; 339:39-46BB

Abstract

Prolonged exposure to inhaled anesthetics may lead to postoperative cognitive dysfunction (POCD). Nevertheless, the underlying mechanisms are not known. Hypoxia-inducible factor-1α (HIF-1α) and its target gene vascular endothelial growth factor (VEGF) were shown to be activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1α in isoflurane-induced blood-brain barrier (BBB) disruption and resultant cognitive impairment. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in vascular permeability, and disrupted BBB ultrastructure were accompanied by the degradation of tight junction proteins occludin and collagen type IV in brain blood vessels. Increases in HIF-1α and VEGF proteins and activation of MMP-2 in the hippocampus were also observed in the hippocamp of isoflurane-exposed rats compared with control rats. Pharmacological inhibition of HIF-1α activation by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) markedly suppressed the expression of HIF-1α, VEGF and MMP-2, and mitigated the severity of BBB disruption.YC-1 pretreatment also significantly attenuated isoflurane-induced cognitive deficits in the Morris water maze task. Overall, our results demonstrate that hippocampal HIF-1α/VEGF signaling seems to be the upstream mechanism of isoflurane-induced cognitive impairment, and provides apotential preventive and therapeutic target for POCD.

Authors+Show Affiliations

Department of Anesthesiology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China; Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Anesthesiology, General Hospital of Ningxia Medcial University Ningxia 750004, China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: zhongyf@bjmu.edc.Neuroscience Research Institute and Department of Neurobiology, Peking University, Beijing 100191, China. Electronic address: dchui@bjmu.edu.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China. Electronic address: puthmzk@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28887194

Citation

Cao, Yiyun, et al. "Hypoxia-inducible Factor-1α Is Involved in Isoflurane-induced Blood-brain Barrier Disruption in Aged Rats Model of POCD." Behavioural Brain Research, vol. 339, 2018, pp. 39-46.
Cao Y, Li Z, Li H, et al. Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD. Behav Brain Res. 2018;339:39-46.
Cao, Y., Li, Z., Li, H., Ni, C., Li, L., Yang, N., ... Guo, X. (2018). Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD. Behavioural Brain Research, 339, pp. 39-46. doi:10.1016/j.bbr.2017.09.004.
Cao Y, et al. Hypoxia-inducible Factor-1α Is Involved in Isoflurane-induced Blood-brain Barrier Disruption in Aged Rats Model of POCD. Behav Brain Res. 2018 Feb 26;339:39-46. PubMed PMID: 28887194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD. AU - Cao,Yiyun, AU - Li,Zhengqian, AU - Li,Hongping, AU - Ni,Cheng, AU - Li,Lunxu, AU - Yang,Ning, AU - Shi,Chengmei, AU - Zhong,Yanfeng, AU - Cui,Dehua, AU - Guo,Xiangyang, Y1 - 2017/09/05/ PY - 2017/06/17/received PY - 2017/08/25/revised PY - 2017/09/02/accepted PY - 2017/9/10/pubmed PY - 2018/8/8/medline PY - 2017/9/10/entrez KW - Blood-brain barrier KW - Hypoxia-inducible factor-1α KW - Isoflurane KW - Postoperative cognitive dysfunction SP - 39 EP - 46 JF - Behavioural brain research JO - Behav. Brain Res. VL - 339 N2 - Prolonged exposure to inhaled anesthetics may lead to postoperative cognitive dysfunction (POCD). Nevertheless, the underlying mechanisms are not known. Hypoxia-inducible factor-1α (HIF-1α) and its target gene vascular endothelial growth factor (VEGF) were shown to be activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1α in isoflurane-induced blood-brain barrier (BBB) disruption and resultant cognitive impairment. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in vascular permeability, and disrupted BBB ultrastructure were accompanied by the degradation of tight junction proteins occludin and collagen type IV in brain blood vessels. Increases in HIF-1α and VEGF proteins and activation of MMP-2 in the hippocampus were also observed in the hippocamp of isoflurane-exposed rats compared with control rats. Pharmacological inhibition of HIF-1α activation by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) markedly suppressed the expression of HIF-1α, VEGF and MMP-2, and mitigated the severity of BBB disruption.YC-1 pretreatment also significantly attenuated isoflurane-induced cognitive deficits in the Morris water maze task. Overall, our results demonstrate that hippocampal HIF-1α/VEGF signaling seems to be the upstream mechanism of isoflurane-induced cognitive impairment, and provides apotential preventive and therapeutic target for POCD. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/28887194/Hypoxia_inducible_factor_1α_is_involved_in_isoflurane_induced_blood_brain_barrier_disruption_in_aged_rats_model_of_POCD_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(17)31022-7 DB - PRIME DP - Unbound Medicine ER -