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

Ye, Lixia; Wang, Xue; Cai, Chenchen; Zeng, Shanshan; Bai, Junjie; Guo, Kaiming; Fang, Mingchu; Hu, Jian; Liu, Huan; Zhu, Li; Liu, Fei; Wang, Dongxue; Hu, Yingying; Pan, Shulin; Li, Xiaokun; Lin, Li; Lin, Zhenlang

doi:10.1016/j.expneurol.2019.02.013

Cited by 61 publications

(47 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Current evidence suggests that activation of the PI3K/Akt and its downstream pathways suppresses neuronal apoptosis in models of HI brain injury (Tu et al, 2018) and under OGD conditions (Ye et al, 2019). GSK3β is a serine/threonine protein kinase with broad expression and one of the downstream targets of Akt.…”

Section: Discussionmentioning

confidence: 99%

“…The PI3K inhibitor LY294002 (Selleck, Shanghai, China) was dissolved in 1% dimethyl sulfoxide to further evaluate whether liraglutide activated the PI3K/Akt/GSK3β pathway. Five microliters of LY294002 (50 nmol/kg; Ye et al, 2019) was administered via intracerebroventricular injection 30 min prior to HI using a stereotaxic apparatus (RWD, Shenzhen, China). LY294002 was injected into the lateral ventricle (2 mm rostral, 1.5 mm outside the bregma, and 2.5 mm below the skull; Zhou et al, 2017) at a speed of 1 µl/min.…”

Section: Neonatal Hypoxic-ischemic Brain Injury Model and Administratmentioning

confidence: 99%

“…The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway participates in a diversity of physiological and pathogenetic processes, such as cell apoptosis, proliferation, and differentiation. Some research studies have demonstrated that this signaling pathway protects neurons from apoptosis in different brain diseases (Ye et al, 2019). Glycogen synthase kinase-3β (GSK3β), one of the downstream targets of activated Akt, has been closely associated with energy metabolism, body shape development, and nerve cell development.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Zeng

Bai

Jiang

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Neonatal hypoxic-ischemic (HI) brain injury is a detrimental disease, which results in high mortality and long-term neurological deficits. Nevertheless, the treatment options for this disease are limited. Thus, the aim of the present study was to assess the role of liraglutide in neonatal HI brain injury in rats and investigate the associated mechanisms. The results showed that treatment with liraglutide significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Moreover, treatment with liraglutide inhibited apoptosis and promoted neuronal survival both in the rat model and following oxygen-glucose deprivation (OGD) insult. LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), partially reversed these therapeutic effects, suggesting that the PI3K/protein kinase B (Akt) pathway was involved. In conclusion, our data revealed that treatment with liraglutide exerts neuroprotection after neonatal HI brain injury via the PI3K/Akt/glycogen synthase kinase-3β (GSK3β) pathway and may be a promising therapy for this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Neonatal Hypoxic-ischemic Brain Injury Model and Administratmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Zeng

Bai

Jiang

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Primary cortical neurons were prepared from embryonal brains (16-18 d) of Sprague-Dawley rats as we previously described [33]. Briefly, the separated cortices were digested by 0.25% trypsin-EDTA (Invitrogen, California, USA), and were filtered by cell strainer.…”

Section: Primary Cortical Neuron Culturesmentioning

confidence: 99%

“…Given the amelioration of brain atrophy after administration of exogenous rhFGF21 [33], we hypothesized that endogenous FGF21 was capable of attenuating neurological deficits. There were no differences in appearance between wild-type (WT) and FGF21 KO mice (Fig.…”

Section: Fgf21 Deficiency Increases Brain Atrophy and Aggravates Neurmentioning

confidence: 99%

Microglia-derived FGF21 as a modulator of astrocytic phenotype and cerebral ischemia injury

Liu¹,

Wang²,

Zhu³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Fibroblast growth factor 21 (FGF21) is an important neuroprotective factor in the central nervous system (CNS), and it has been reported that FGF21 can protect against cerebral ischemia during the acute phase. However, the possible effects of FGF21 on ischemic brains and the interactions between FGF21 and nonneuronal cells have not been examined. Thus, the aim of this study was to elucidate the protective effects of endogenous FGF21 in ischemic brains.Methods: In this study, in vivo ischemia/reperfusion injury mouse model established by transient middle cerebral artery occlusion (MCAO)/reperfusion and in vitro cell models of oxygen/glucose deprivation (OGD)/reoxygenation (R) were used. Western blot analysis, RT-PCR, double immunofluorescence staining, immunohistochemistry, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, neurobehavioral tests, cell counting kit-8 (CCK-8) assay and high-throughput gene sequencing were employed to explore the mechanism by which FGF21 unleash neuroprotective effort of astrocyte phenotype shifts in ischemic stroke.Results: We found that cortical FGF21 expression significantly increased after MCAO/reperfusion, peaking at 7 d. Ischemia-activated microglia were the main sources of endogenous FGF21 in brain tissue. However, FGF21 deficiency aggravated brain injury and slowed neurological functional recovery in FGF21 knockout mice. The in vitro and vivo studies revealed that FGF21 could activate astrocytes and mediate astrocytic phenotype. FGF21-activated astrocytes contributed to neuronal survival and synaptic protein upregulation after ischemia.Conclusion: Collectively, our data indicate that FGF21 plays vital roles in alleviating ischemic brain by mediating the manifestation of potentially pro-recovery astrocytic phenotypes. Therefore, modulation of FGF21 is a potential target strategy for stroke.

show abstract

Schizophrenia predisposition gene Unc-51-like kinase 4 for the improvement of cerebral ischemia/reperfusion injury

Luo

Yang

2022

Mol Biol Rep

View full text Add to dashboard Cite

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

Cited by 61 publications

References 58 publications

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Microglia-derived FGF21 as a modulator of astrocytic phenotype and cerebral ischemia injury

Schizophrenia predisposition gene Unc-51-like kinase 4 for the improvement of cerebral ischemia/reperfusion injury

Contact Info

Product

Resources

About