Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice

Abstract

FGF10 is a member of fibroblast growth factors (FGFs). We previously showed that FGF10 protects neuron against oxygen-glucose deprivation injury in vitro; however, the effect of FGF10 in ischemic stroke in vivo is unknown. In the present study, we showed that FGF10 was mainly expressed in neurons but not astrocytes, and detected FGF10 in mouse cerebrospinal fluid. The FGF10 levels in neurons culture medium and cell lysate were much higher than those in astrocytes. FGF10 expression in brain tissue and FGF10 level in CSF were increased in mouse middle cerebral artery occlusion (MCAO) model. Administration of FGF10 into lateral cerebroventricle not only decreased MCAO-induced brain infarct volume and neurological deficit, but also reduced the number of TUNEL-positive cells and activities of Caspases. Moreover, FGF10 treatment depressed the triggered inflammatory factors (TNF-α and IL-6) and NF-κB signaling pathway, and increased phosphorylation of PI3K/Akt signaling pathway. Blockade of PI3K/Akt signaling pathway by wortmannin and Akt1/2-kinase inhibitor, partly compromised the neuroprotection of FGF10. However, blockade of PI3K/Akt signaling pathway did not impair the anti-inflammation action of FGF10. Collectively, our results demonstrate that neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia–Reperfusion Injury

“…Despite the current clinical advances in prevention and treatment, the morbidity and mortality of AKI in hospitalized patients remain very high (Basile et al, 2012;Winterberg and Lu, 2012). As a crucial mesenchymal-epithelial signaling growth factor in embryonic development, tissue repair, and regeneration, the role of FGF10 has been investigated in several disease conditions such as cerebral ischemia injury, pulmonary fibrosis, and wound healing (Li et al, 2016;Chen et al, 2017;Chao et al, 2017;El Agha et al, 2017). However, whether FGF10 is capable of delivering a protective effect on AKI in rat model of I/R injury is still unclear.…”

Therapeutic effects of dietary intervention on neuroinflammation and brain metabolism in a rat model of photothrombotic stroke

“…The preischemic dietary intervention caused partial reversal of astrocyte activation on day 21 (SI-pre 21 : 1.54 ± 0.06, SI-pre 21 vs SC 21 P < 0.05, SI-pre 21 vs CC 21 P < 0.05, SI-post 21 vs SI-pre 21 : P < 0.05). [ 18 F]FDG PET imaging demonstrated a trend toward a reduction in whole brain metabolism due to ischemia on day 7 (CC 7 = 1.47 ± 0.02 vs SC 7 = 1.31 ± 0.02, P = 0.06, Figure 6), but not anymore on day 21…”

“…30 The test was performed in light phase and recorded on video. [ 18 F]FDG PET scans were performed using a dedicated small animal PET scanner (Focus 220, Siemens Medical Solutions USA, Malvern, PA). The body temperature of the rats was maintained with heating pads, eye salve was applied onto the eyes to prevent dehydration, and heart rate and blood oxygen levels were monitored with a BioVet system (M2M Imaging, Cleveland, OH).…”

Relationship between depression and blood cytokine levels in lung cancer patients

“…IL-1β, IL-6, IL-10, TNF-α coud act through the hypothalamus pituitary adrenal axis (HPA) involved in the pathogenesis of depression [8,9]. IL-6, IL-10, an increased level of TNF-α activity can induce the secretion of adrenal hormone releasing hormone by the hypothalamus [24][25][26], resulting in excessive HPA activity and leading to depressive symptoms and depression in patients with lung cancer. IL-8 level was found to be relatively elevated in lung cancer patients as compared to healthy individuals, but but no significant correlation with depression level was found.…”