FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/β-klotho

Experimental Neurology
Lixia YeZhenlang Lin

Abstract

Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown that fibroblast growth factor 21 (FGF21) has a potential neuroprotective effect against brain injury. However, the effect of FGF21 on neonatal HI brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether recombinant human FGF21 (rhFGF21) could exert a neuroprotective effect after HI and explore the associated mechanism. The results showed that the rhFGF21 treatment remarkably reduced the infarct volume, ameliorated the body weight and improved the tissue structure after HI in neonatal rats. In addition, the rhFGF21 treatment lengthened the running endurance times in the rotarod test and decreased the mean escape latencies and increased the number of platform crossings in the Morris water maze test at 21 d post-HI insult. In contrast, the FGFR1 inhibitor PD173074 and PI3K inhibitor LY294002 partially reversed these therapeutic effects. In isolated primary cortical neurons, the rhFGF21 treatment p...Continue Reading

Citations

Jan 1, 2020·PloS One·Valerie ZabalaJennifer A Sanders
Aug 25, 2020·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jia LiYong-Sheng Wang
Jul 17, 2020·Frontiers in Pharmacology·Zhengtai ChenWeiyang Gao
Apr 8, 2020·BioResearch Open Access·Walter H MoosXiaohong Chen
Sep 15, 2020·Frontiers in Pediatrics·Lina ShiXiuyong Cheng
Jan 8, 2021·Molecular Neurobiology·Travis C JacksonPatrick M Kochanek
Apr 6, 2021·Frontiers in Genetics·S Akila Parvathy DharshiniM Michael Gromiha
Aug 14, 2021·Cell Stress & Chaperones·Elham RazaniDavood Bashash
Jul 15, 2021·Critical Care Medicine·Heidi J DaltonRobert H Bartlett

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