Chapter 15 - Regeneration of Injured Spinal Cord and Peripheral Nerves by α-Gal Nanoparticles

Abstract

This chapter describes a hypothetical method for induction of injured nerve regeneration by application of α-gal nanoparticles to the lesion sites. α-Gal nanoparticles are submicroscopic liposomes that present many α-gal epitopes. Regeneration of severed neurons in the spinal cord and in peripheral nerves is dependent on axonal sprouts growing across the lesion gap and reconnecting with the endoneurial tubes of the distal axonal segment (referred to as “distal segments”). The growth of axonal sprouts occurs along newly formed capillaries and other small blood vessels from which the sprouts receive oxygen and nutrients. Because the axonal sprouts grow without specific orientation, the reconnection with the distal segments is a random rare event, which may occur if the axonal sprouts accidentally “find” these segments. If the regeneration is not successful within few weeks post injury, the nerve damage becomes permanent because of fibrosis that converts the lesion into scar segments and the complete degradation of the distal segments. Induction of extensive neovascularization in the nerve lesion site by administration of vascular endothelial growth factor (VEGF) was found to increase axonal sprouting and thus, increases the probability for regeneration by axonal sprouts reconnecting distal segments. It is suggested that α-gal nanoparticles applied to spinal cord injuries and to other nerve lesions will bind anti-Gal, activate complement, and generate complement cleavage chemotactic peptides that will induce extensive recruitment of macrophages. Macrophages reaching the α-gal nanoparticles within the lesions bind the anti-Gal coated nanoparticles via Fc/Fcγ receptor interaction and are polarized into becoming M2 macrophages that secrete VEGF and other prohealing cytokines/growth factors. The secreted VEGF induces neovascularization within the lesion resulting in extensive growth of many axonal sprouts, which ultimately increase the probability of severed axons reconnecting with the distal segments and regeneration of the injured nerve prior to formation of scar tissue within the lesion.