The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

Abstract

The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [F]-fluoro-L-thymidine ([F]FLT) to visualize endogenous NSC in vivo. FGL significantly increased endogenous NSC mobilization in the neurogenic niches as evidenced by in vivo and ex vivo methods, and it induced remyelination. Moreover, FGL affected neuroinflammation. Extending previous in vitro results, our data show that the NCAM mimetic peptide FGL mobilizes endogenous NSC after focal ischemia and enhances regeneration by amplifying remyelination and modulating neuroinflammation via affecting microglia. Results suggest FGL as a promising candidate to promote recovery after stroke.

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients

“…Neuroplasticity is closely related to neurogenesis, wherein fully functioning neuronal cells are generated, resulting from the differentiation of neuronal stem cells (NSCs) present in the adult, fully formed brain. NSCs are characterized by the ability of indefinite mitotic division, potential divisions, and to differentiate into the appropriate morphological phenotype ( Klein et al, 2016 ). The process of neurogenesis occurs in certain brain structures throughout life, nevertheless the rate of proliferation and the ability of the newly formed neurons to survive to reduce with age.…”

Pharmacological approaches promoting stem cell-based therapy following ischemic stroke insults

“…CXCR4 antagonist AMD3100 and CX549 mobilized bone marrow hematopoietic stem cells (HSCs) for transplantation by reducing neuroinflammation in stroke brain [114] . The neural cell adhesion molecule-derived peptide FG loop significantly increased endogenous NSC mobilization in the neurogenic niches, which is associated with the modulation of the activation of microglia and modulation of neuroinflammation [115] . rIL-6 significantly increased the proliferation of NPCs in the ipsilateral SVZ [116] .…”

Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis

“…While the transplantation of exogenous NSCs involves the risks of cellular death, failed integration and formation of tumors, endogenous NSCs can be involved in the regeneration process after stroke without any risk. However, previous experimental studies proved the intrinsic potential of endogenous NSCs to be insufficient, therefore external stimuli might be required to exploit their full therapeutic potential [49].…”

“…Moreover, anti-inflammatory effects of FGL administration have been postulated, as NCAM mimetic modulates the M1/M2 polarization of microglia with further protective effects. Thus, NCAM-FGL presents the potential to enhance the cerebral self-repair mechanism after the acute ischemic event [49].…”