The Effect of RADA16-I and CDNF on Neurogenesis and Neuroprotection in Brain Ischemia-Reperfusion Injury

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163360

Authors

Xingyu Liu

Haiyuan Ren

Ai Peng

Haoyang Cheng

Jiahao Chen

Xue Xia

Ting Liu

Xiaojing Wang

Affiliations

Soon will be listed here.

Abstract

Scaffold materials, neurotrophic factors, and seed cells are three elements of neural tissue engineering. As well-known self-assembling peptide-based hydrogels, RADA16-I and modified peptides are attractive matrices for neural tissue engineering. In addition to its neuroprotective effects, cerebral dopamine neurotrophic factor (CDNF) has been reported to promote the proliferation, migration, and differentiation of neural stem cells (NSCs). However, the role of RADA16-I combined with CDNF on NSCs remains unknown. First, the effect of RADA16-I hydrogel and CDNF on the proliferation and differentiation of cultured NSCs was investigated. Next, RADA16-I hydrogel and CDNF were microinjected into the lateral ventricle (LV) of middle cerebral artery occlusion (MCAO) rats to activate endogenous NSCs. CDNF promoted the proliferation of NSCs, while RADA16-I induced the neural differentiation of NSCs in vitro. Importantly, both RADA16-I and CDNF promoted the proliferation, migration, and differentiation of endogenous NSCs by activating the ERK1/2 and STAT3 pathways, and CDNF exerted an obvious neuroprotective effect on brain ischemia-reperfusion injury. These findings provide new information regarding the application of the scaffold material RADA16-I hydrogel and the neurotrophic factor CDNF in neural tissue engineering and suggest that RADA16-I hydrogel and CDNF microinjection may represent a novel therapeutic strategy for the treatment of stroke.

Citing Articles

Peptide-Based Biomaterials for Combatting Infections and Improving Drug Delivery.

Lombardi L, Li J, Williams D Pharmaceutics. 2024; 16(11).

PMID: 39598591 PMC: 11597775. DOI: 10.3390/pharmaceutics16111468.

Innovative hydrogel-based therapies for ischemia-reperfusion injury： bridging the gap between pathophysiology and treatment.

Wang W, Tai S, Tao J, Yang L, Cheng X, Zhou J Mater Today Bio. 2024; 29:101295.

PMID: 39493810 PMC: 11528235. DOI: 10.1016/j.mtbio.2024.101295.

Impact of subthalamic nucleus deep brain stimulation at different frequencies on neurogenesis in a rat model of Parkinson's disease.

Wu Z, Ren Z, Gao R, Sun K, Sun F, Liu T Heliyon. 2024; 10(10):e30730.

PMID: 38784548 PMC: 11112288. DOI: 10.1016/j.heliyon.2024.e30730.

Release systems based on self-assembling RADA16-I hydrogels with a signal sequence which improves wound healing processes.

Dzierzynska M, Sawicka J, Deptula M, Sosnowski P, Sass P, Peplinska B Sci Rep. 2023; 13(1):6273.

PMID: 37072464 PMC: 10113214. DOI: 10.1038/s41598-023-33464-w.

Perspective insights into hydrogels and nanomaterials for ischemic stroke.

Yu Q, Jian Z, Yang D, Zhu T Front Cell Neurosci. 2023; 16:1058753.

PMID: 36761147 PMC: 9902513. DOI: 10.3389/fncel.2022.1058753.

References

Ortinau S, Schmich J, Block S, Liedmann A, Jonas L, Weiss D . Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells. Biomed Eng Online. 2010; 9:70. PMC: 2996398. DOI: 10.1186/1475-925X-9-70. View

Lindholm P, Saarma M . Novel CDNF/MANF family of neurotrophic factors. Dev Neurobiol. 2010; 70(5):360-71. DOI: 10.1002/dneu.20760. View

Lang A, Gill S, Patel N, Lozano A, Nutt J, Penn R . Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol. 2006; 59(3):459-66. DOI: 10.1002/ana.20737. View

Yan Y, Sailor K, Lang B, Park S, Vemuganti R, Dempsey R . Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab. 2006; 27(6):1213-24. DOI: 10.1038/sj.jcbfm.9600432. View

Wang X, Sun T, Kong L, Shang Z, Yang K, Zhang Q . Gypenosides pre-treatment protects the brain against cerebral ischemia and increases neural stem cells/progenitors in the subventricular zone. Int J Dev Neurosci. 2013; 33:49-56. DOI: 10.1016/j.ijdevneu.2013.12.001. View

Webb D, Donais K, Whitmore L, Thomas S, Turner C, Parsons J . FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol. 2004; 6(2):154-61. DOI: 10.1038/ncb1094. View

Yla-Outinen L, Joki T, Varjola M, Skottman H, Narkilahti S . Three-dimensional growth matrix for human embryonic stem cell-derived neuronal cells. J Tissue Eng Regen Med. 2012; 8(3):186-94. DOI: 10.1002/term.1512. View

Huang C, Jacobson K, Schaller M . MAP kinases and cell migration. J Cell Sci. 2004; 117(Pt 20):4619-28. DOI: 10.1242/jcs.01481. View

Schmidt C, Leach J . Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng. 2003; 5:293-347. DOI: 10.1146/annurev.bioeng.5.011303.120731. View

10.

Lindholm P, Voutilainen M, Lauren J, Peranen J, Leppanen V, Andressoo J . Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature. 2007; 448(7149):73-7. DOI: 10.1038/nature05957. View

11.

Sun T, Wang X, Xie S, Zhang D, Wang X, Li B . A comparison of proliferative capacity and passaging potential between neural stem and progenitor cells in adherent and neurosphere cultures. Int J Dev Neurosci. 2011; 29(7):723-31. DOI: 10.1016/j.ijdevneu.2011.05.012. View

12.

Ng D, Lin B, Lim C, Huang G, Zhang T, Poli V . Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin. J Cell Biol. 2006; 172(2):245-57. PMC: 2063554. DOI: 10.1083/jcb.200503021. View

13.

Yokoi H, Kinoshita T, Zhang S . Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proc Natl Acad Sci U S A. 2005; 102(24):8414-9. PMC: 1150805. DOI: 10.1073/pnas.0407843102. View

14.

Lendahl U, Zimmerman L, McKay R . CNS stem cells express a new class of intermediate filament protein. Cell. 1990; 60(4):585-95. DOI: 10.1016/0092-8674(90)90662-x. View

15.

Lin C, Chen L . Cerebral dopamine neurotrophic factor promotes the proliferation and differentiation of neural stem cells in hypoxic environments. Neural Regen Res. 2020; 15(11):2057-2062. PMC: 7716052. DOI: 10.4103/1673-5374.282262. View

16.

Zhang G, Wang L, Liu X, Zhang Y, Hu M, Liu L . Cerebral Dopamine Neurotrophic Factor (CDNF) Has Neuroprotective Effects against Cerebral Ischemia That May Occur through the Endoplasmic Reticulum Stress Pathway. Int J Mol Sci. 2018; 19(7). PMC: 6073452. DOI: 10.3390/ijms19071905. View

17.

Davis A, Temple S . A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature. 1994; 372(6503):263-6. DOI: 10.1038/372263a0. View

18.

Jin K, Sun Y, Xie L, Peel A, Mao X, Batteur S . Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci. 2003; 24(1):171-89. DOI: 10.1016/s1044-7431(03)00159-3. View

19.

Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V . Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells. 2005; 24(3):739-47. DOI: 10.1634/stemcells.2005-0281. View

20.

Sheu J, Kulhanek D, Eckenstein F . Differential patterns of ERK and STAT3 phosphorylation after sciatic nerve transection in the rat. Exp Neurol. 2000; 166(2):392-402. DOI: 10.1006/exnr.2000.7508. View