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Association of Impaired Hypoxia‐Inducible Factor‐1 Transcriptional Activity with Severer Brain Injury in Aged Rats in Comparison with Young Rats after Acute Ischemic Stroke
Author(s) -
Guo Yingjia,
Li Xianglong,
Han Pengfei,
Xiao Ying,
Zhu Ping,
Gou Zhaoyu,
Kang Y. James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.993.6
Subject(s) - medicine , neuroprotection , hypoxia (environmental) , stroke (engine) , young adult , ischemia , endocrinology , angiogenesis , apoptosis , anesthesia , physiology , biology , mechanical engineering , biochemistry , chemistry , organic chemistry , oxygen , engineering
Aged mammals in comparison with young suffer severer damage post ischemic stroke, and hypoxia‐inducible factor‐1 (HIF‐1) activation is neuroprotective in ischemic stroke. The present study was undertaken to investigate whether there is a difference in HIF‐1 between aged and young rats and its association with the degree in brain damage post ischemic stroke. Aged (18–20 months) and young (3–4 months) male Sprague‐Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 60‐min, followed by reperfusion for 3, 7, 14, or 21 days. There was no significant difference in the infarct volume in the brain between aged and young rats 3 days after MCAO, but the infarct volume in the aged was significantly larger than in the young animals 21 days after MCAO. The overall survival rate in the aged was significantly lower than in the young rats. In addition, delayed body weight gain, retarded neurobehavioral recovery, and depressed angiogenesis were observed in the aged rats compared to the young at 3, 7, and 21 days after MCAO. There was no significant difference in the protein levels of HIF‐1 accumulated in the ischemic area between the aged and the young rats at 3 days after MCAO, however, the HIF‐1 transcriptional activity was significantly suppressed, along with increased apoptotic cell death, in the aged rats. Furthermore, the levels of mRNAs involved in modulating HIF‐1α stabilization and HIF‐1 target genes were dramatically different between aged and young rats. These findings thus revealed the association of impaired HIF‐1 transcriptional activity with the delayed neurobehavioral recovery after focal ischemic stroke in aged rats. Support or Funding Information The National Basic Research Program of China (973 Program Grant no. 2013CB530702).