Immobilized Concentration Gradients of Neurotrophic Factors Guide Neurite Outgrowth of Primary Neurons in Macroporous Scaffolds

2006 ◽  
Vol 12 (2) ◽  
pp. 267-278 ◽  
Author(s):  
Kathryn Moore ◽  
Margaret Macsween ◽  
Molly Shoichet
Keyword(s):  
Neurite Outgrowth ◽  
Neurotrophic Factors ◽  
Primary Neurons ◽  
Concentration Gradients

scholarly journals EphA4 Obstructs Spinal Cord Neuron Regeneration by Promoting Excessive Activation of Astrocytes

2021 ◽  
Author(s):  
Xiaogang Chen ◽  
Lin Zhang ◽  
Fu Hua ◽  
Yu Zhuang ◽  
Huan Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Neurotrophic Factors ◽  
Cellular Localization ◽  
Axon Regeneration ◽  
Chondroitin Sulphate ◽  
Cortical Cell ◽  
Inflammatory Factors ◽  
Cord Injury

AbstractStudies have found that molecular targets that regulate tissue development are also involved in regulating tissue regeneration. Erythropoietin-producing hepatocyte A4 (EphA4) not only plays a guiding role in neurite outgrowth during the development of the central nervous system (CNS) but also induces injured axon retraction and inhibits axon regeneration after spinal cord injury (SCI). EphA4 targets several ephrin ligands (including ephrin-A and ephrin-B) and is involved in cortical cell migration, axon guidance, synapse formation and astrocyte function. However, how EphA4 affects axon regeneration after SCI remains unclear. This study focuses on the effect and mechanism of EphA4-regulated astrocyte function in neuronal regeneration after SCI. Our research found that EphA4 expression increased significantly after SCI and peaked at 3 days post-injury; accordingly, we identified the cellular localization of EphA4 and ephrin-B ligands in neurons and astrocytes after SCI. EphA4 was mainly expressed on the surface of neurons, ephrin-B1 and ephrin-B3 were mainly localized on astrocytes, and ephrin-B2 was distributed on both neurons and astrocytes. To further elucidate the effect of EphA4 on astrocyte function after SCI, we detected the related cytokines secreted by astrocytes in vivo. We found that the levels of neurotrophic factors including nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) increased significantly after SCI (NGF peaked at 3 days and bFGF peaked at 7 days); the expression of laminin and fibronectin increased gradually after SCI; the expression of inflammatory factors [interleukin (IL)-1β and IL-6] increased significantly from 4 h to 7 days after SCI; and the levels of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and chondroitin sulphate proteoglycan (CSPG), the main component of glial scars, both peaked at 7 days after SCI. Using a damaged astrocyte model in vitro, we similarly found that the levels of related cytokines increased after injury. Consequently, we observed the effect of damaged astrocytes on neurite outgrowth and regeneration, and the results showed that damaged astrocytes hindered neurite outgrowth and regeneration; however, the inhibitory effect of injured astrocytes on neurite regeneration was reduced following ephrin-B receptor knockdown or inflammatory inhibition at 24 h after astrocyte injury. Our results showed that EphA4 regulates the secretion of neurotrophic factors, adhesion molecules, inflammatory factors and glial scar formation by binding with the ligand ephrin-B located on the surface of astrocytes. EphA4 affects neurite outgrowth and regeneration after SCI by regulating astrocyte function.

scholarly journals c-Jun Gene-Modified Schwann Cells: Upregulating Multiple Neurotrophic Factors and Promoting Neurite Outgrowth

2015 ◽  
Vol 21 (7-8) ◽  
pp. 1409-1421 ◽  
Author(s):  
Liangliang Huang ◽  
Xin Quan ◽  
Zhongyang Liu ◽  
Teng Ma ◽  
Yazhen Wu ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Schwann Cells ◽  
Neurotrophic Factors

Alpha-synuclein promotes early neurite outgrowth in cultured primary neurons

2013 ◽  
Vol 120 (9) ◽  
pp. 1331-1343 ◽  
Author(s):  
Guangwei Liu ◽  
Peng Wang ◽  
Xin Li ◽  
Yaohua Li ◽  
Shengli Xu ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Alpha Synuclein ◽  
Primary Neurons

scholarly journals The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Ouada Nebie ◽  
David Devos ◽  
Valérie Vingtdeux ◽  
Lassina Barro ◽  
Jean-Christophe Devedjian ◽  
...  
Keyword(s):  
Neurotrophic Factors ◽  
Industrial Development ◽  
Human Platelet ◽  
Neuron Specific Enolase ◽  
Source Material ◽  
Neuroprotective Activity ◽  
Primary Neurons ◽  
Platelet Concentrates ◽  
Heat Treated ◽  
Platelet Pellet

Abstract Background Effective neurorestorative therapies of neurodegenerative diseases must be developed. There is increasing interest in using human platelet lysates, rich in neurotrophic factors, as novel disease-modifying strategy of neurodegeneration. To ensure virus safety, pathogen reduction treatments should be incorporated in the preparation process of the platelet concentrates used as source material. We therefore investigated whether platelet concentrates (PC) pathogen-inactivated using a licensed photo-inactivation treatment combining photosensitive psoralen (amotosalen) and UVA irradiation (Intercept) can serve as source material to prepare platelet lysates with preserved neuroprotective activity in Parkinson’s disease models. Methods Intercept treated-PCs were centrifuged, when reaching expiry day (7 days after collection), to remove plasma and platelet additive solution. The platelet pellet was re-suspended and concentrated in phosphate buffer saline, subjected to 3 freeze-thaw cycles (− 80 °C/37 °C) then centrifuged to remove cell debris. The supernatant was recovered and further purified, or not, by heat-treatment as in our previous investigations. The content in proteins and neurotrophic factors was determined and the toxicity and neuroprotective activity of the platelet lysates towards LUHMES cells or primary cortical/hippocampal neurons were assessed using ELISA, flow cytometry, cell viability and cytotoxicity assays and proteins analysis by Western blot. Results Platelet lysates contained the expected level of total proteins (ca. 7–14 mg/mL) and neurotrophic factors. Virally inactivated and heat-treated platelet lysates did not exert detectable toxic effects on neither Lund human mesencephalic dopaminergic LUHMES cell line nor primary neurons. When used at doses of 5 and 0.5%, they enhanced the expression of tyrosine hydroxylase and neuron-specific enolase in LUHMES cells and did not significantly impact synaptic protein expression in primary neurons, respectively. Furthermore, virally-inactivated platelet lysates tested were found to exert very strong neuroprotection effects on both LUHMES and primary neurons exposed to erastin, an inducer of ferroptosis cell death. Conclusion Outdated Intercept pathogen-reduced platelet concentrates can be used to prepare safe and highly neuroprotective human heat-treated platelet pellet lysates. These data open reassuring perspectives in the possibility to develop an effective biotherapy using virally-inactivated platelet lysates rich in functional neurotrophins for neuroregenerative medicine, and for further bio-industrial development. However, the data should be confirmed in animal models. Graphical abstract

scholarly journals Combination Effects of Curcumin and Aqueous Extract of Lignosus rhinocerotis Mycelium on Neurite Outgrowth Stimulation Activity in PC-12 Cells

2013 ◽  
Vol 8 (6) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Priscilla A. John ◽  
Kah - Hui Wong ◽  
Murali Naidu ◽  
Vikineswary Sabaratnam ◽  
Pamela David
Keyword(s):  
Small Molecules ◽  
Neurite Outgrowth ◽  
Aqueous Extract ◽  
Neurotrophic Factors ◽  
Neuronal Function ◽  
Pc 12 Cells ◽  
Neurite Extension ◽  
High Concentrations ◽  
Lignosus Rhinocerotis ◽  
Stimulation Of

Neurotrophic factors are necessary for neuronal navigation to form viable neuronal networks. These factors are high molecular weight polypeptides that cannot cross the blood brain-barrier. Therefore, small molecules from mushrooms and plants are utilized to maintain neuronal function or up-regulate neurotrophic factors. The present study investigated whether a combination of Lignosus rhinocerotis mycelium aqueous extract and curcumin was more effective than L. rhinocerotis mycelium or curcumin alone in the stimulation of neurite outgrowth of PC-12 cells. The maximum neurite extension for L. rhinocerotis and curcumin was at 21.1% at 20 μg/mL and 29.5% at 10 μg/mL, respectively. Combining 20 μg/mL of L. rhinocerotis with one μg/mL curcumin gave 27.2% neurite extension. This combination was preferred because high concentrations of curcumin were toxic to cells. In the combination, 20 μg/mL of L. rhinocerotis enhanced neurite outgrowth activity at a lower dosage of curcumin at one μg/mL, and produced a comparable percentage of neurite outgrowth stimulation activity to L. rhinocerotis and curcumin alone in PC-12 cells.

scholarly journals Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniel Santos ◽  
Francisco Gonzalez-Perez ◽  
Xavier Navarro ◽  
Jaume del Valle
Keyword(s):  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Collagen Matrix ◽  
High Dose ◽  
Organotypic Cultures ◽  
High Doses ◽  
Dose Dependent

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

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