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

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.

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

“…Moreover recently RADA16-I peptide was studied as a artificial ECM for studying cancer cell behaviours 29 . Delivery of an unmodified RADA16-I hydrogel results in immediate hemostasis, which has been proven by its application on cut wounds on the brain, liver, femoral artery, spinal cord, skin and ischemia–reperfusion injury 30 – 33 . The results showed that RADA16-I alone slightly increased wound closure and reepithelization compared to the control.…”

Water-Soluble, Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells

“…Like neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) has a chemoattractant effect in the migration of neuronal precursor cells along the rostral migratory stream [ 42 ]. Furthermore, for non-classical neurotrophic factors, mesencephalic astrocyte-derived neurotrophic factor (MANF), together with its homolog cerebral dopamine neurotrophic factor (CDNF), can promote the migration of neural progenitor cells in the stroke model [ 43 , 44 ].…”

Perspective insights into hydrogels and nanomaterials for ischemic stroke

“…Neurotrophic factors may also be pivotal elements of neuronal regeneration and neuroprotection. Hydrogel carried with BDNF, and cerebral dopamine neurotrophic factor (CDNF) exerts therapeutic effects on stroke models of rats ( Ravina et al, 2018 ; Liu X. et al, 2022 ). In addition to the common factors, erythropoietin (EPO) also plays a fundamental role in neural development and neuroprotection ( Wakhloo et al, 2020 ).…”