α-Gal Nanoparticles in CNS Trauma: II. Immunomodulation Following Spinal Cord Injury (SCI) Improves Functional Outcomes
10.1007/s13770-023-00616-y
- Author:
Bhavani GOPALAKRISHNAN
1
;
Uri GALILI
;
Megan SAENGER
;
Noah J. BURKET
;
Wendy KOSS
;
Manjari S. LOKENDER
;
Kaitlyn M. WOLFE
;
Samantha J. HUSAK
;
Collin J. STARK
;
Luis SOLORIO
;
Abigail COX
;
August DUNBAR
;
Riyi SHI
;
Jianming LI
Author Information
1. Center for Paralysis Research, Purdue University, West Lafayette, IN 47907, USA
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2024;21(3):437-453
- CountryRepublic of Korea
- Language:EN
-
Abstract:
BACKGROUND:Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-a-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord.
METHODS:α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints.
RESULTS:Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group.
CONCLUSIONS:Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.GRAPHICAL ABSTRACT Putative mechanism of therapeutic action by α-gal nanoparticles. A. Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. B. Recruited M2 macrophages and microglia secrete neuroprotective and prohealing factors to promote tissue repair, neovascularization and axonal regeneration (C.).
