Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation

Wu, Yanqing; Wang, Zhouguang; Cai, Pingtao; Jiang, Ting; Li, Yiyang; Yuan, Yuan; Li, Rui; Khor, Sinan; Lu, Yingfeng; Wang, Jian; Chen, Daqing; Zeng, Qian; Zhong, Ruisheng; Zhang, Hongyu; Lin, Ying‐Chin; Li, Xiaokun; Xiao, Jian

doi:10.1159/000490139

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…In the present study, we either knocked down bFGF or administered OGD to induce morphological and cell viability changes of cultured rat neurons. We found OGD could induce swollen cell bodies and shortened axon length, which was consistent with numerous evidence that OGD treatment could deteriorate the growth of neurons (He et al, 2016;Lin et al, 2015;Liu, Yang, Tian, & Ma, 2016;Wang, Liang, et al, 2014;Wu et al, 2018;Zhang et al, 2014) and it could result in neural damage (Kusumoto et al, 1997;Li, Suo, Liu, Li, & Xue, 2017). Further, we confirmed that bFGF-siRNA had a passive effect on the growth and normal morphology of neurons.…”

Section: Bfgf Plays a Neuroprotective Role In Cultured Primary Cortex Neuronssupporting

confidence: 91%

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

Wang

Xue

et al. 2020

Brain and Behavior

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Introduction Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. Methods We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen–glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL‐1β was examined in bFGF knockdown condition. IL‐1β knockout (KO) rats were generated using CRISPR/Cas9‐mediated technologies. We used an accepted rat model of HI, to assess the effect of IL‐1β deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. Results We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin‐1β (IL‐1β). IL‐1β was up‐regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD‐mediated pathways. We found HI resulted in up‐regulation of IL‐1β mRNA in cortex and hippocampus. IL‐1β KO rats markedly attenuated the impairment of long‐term learning and memory induced by HI. Meanwhile, IL‐1β −/− (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up‐regulated in IL‐1β KO rats. Conclusions We showed that IL‐1β‐mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.

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Section: Bfgf Plays a Neuroprotective Role In Cultured Primary Cortex Neuronssupporting

confidence: 91%

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

Wang

Xue

et al. 2020

Brain and Behavior

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“…The bioactivity of the released NGF from the NGF‐BCT22 was assessed in vitro using PC12 cells co‐cultured with the NGF releasing BCT22. PC12 cells are commonly used to assess NGF bioactivities in vitro since they change phenotype and develop characteristics similar to sympathetic neurons in the presence of NGF in a dose dependent fashion (Das, Freudenrich, & Mundy, ; Wu et al, ).…”

Section: Resultsmentioning

confidence: 99%

Production and evaluation of biosynthesized cellulose tubes as promising nerve guides for spinal cord injury treatment

Stumpf

Tang

Kirkwood

et al. 2020

J Biomedical Materials Res

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Spinal cord injury (SCI) is a central nervous disorder that can result in permanent motor and sensory damage due to a severed communication pathway. Although there is currently no effective treatment, nerve guide tubes have been used to bridge the injured stumps and act as drug delivery systems. In this study, biosynthesized cellulose (BC) nerve guides were prepared, and nerve growth factor (NGF)—a model growth factor—was incorporated into the tubular nerve guide in order to obtain a nerve guide/drug delivery system to assist the regeneration. To achieve this, Gluconacetobacter hansenii was cultivated in a special bioreactor to produce biosynthesized cellulose tubes (BCTs) in situ, and the physical and mechanical properties of the BCTs obtained from different cultivation time points were evaluated. Our results showed that the properties of the BCTs were comparable to those of the native human neural tissues, and that the NGF released from the BCTs was bioactive for at least 7 days as evaluated by PC12 cell cultures in vitro. In summary, this study evaluated the use of BCT as a drug releasing nerve guide, and our results showed that the BCT is an attractive strategy to enhance nerve regeneration after the SCI.

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“…PC12 and SH-SY5Y cells were used to test the suitability of the system. The group containing bFGF and NGF promoted cell growth and proliferation better than those containing only bFGF or NGF [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Biomaterial-Based bFGF Delivery for Nerve Repair

Huang

Liu

2023

Oxidative Medicine and Cellular Longevity

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Diseases in the nervous system are common in the human body. People have to suffer a great burden due to huge economic costs and poor prognosis of the diseases. Many treatment modalities are now available that can make recovery better. Managing nutritional factors is also helpful for such diseases. The basic fibroblast growth factor (bFGF) is one of the major nutritional factors, which plays a crucial role in organogenesis and tissue homeostasis. It plays a role in cell proliferation, migration, and differentiation, thereby regulating angiogenesis and wound healing and repair of the muscle, bone, and nerve. The study on how to improve the stability of bFGF to increase the treatment effect for different diseases has garnered tremendous attention. Biomaterials are the popular methods to improve the stability of bFGF because they are safe for the living body as they are biocompatible. Biomaterials can be loaded with bFGF and delivered locally to achieve the goal of sustained bFGF release. In the present review, we report different types of biomaterials that are used for bFGF delivery for nerve repair and briefly report how the introduced bFGF can function in the nervous system. We aim to provide summative guidance for future studies about nerve injury using bFGF.

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Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation

Cited by 16 publications

References 28 publications

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

Production and evaluation of biosynthesized cellulose tubes as promising nerve guides for spinal cord injury treatment

Biomaterial-Based bFGF Delivery for Nerve Repair

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