Background
Spinal cord injury (SCI) triggers a robust neuroinflammatory response that governs secondary injury mechanisms with both degenerative and pro-regenerative effects. Identifying new immunomodulatory therapies to promote the supportive aspect of immune response is critically needed for the treatment of SCI. We previously demonstrated that SCI
Conclusion
We provide the first evidence of a significant regulatory role for Nrg-1 in neuroinflammation after SCI. Importantly, the present study establishes the promise of systemic Nrg-1 treatment as a candidate immunotherapy for traumatic SCI and other CNS neuroinflammatory conditions.
Methods
We utilized a clinically relevant model of moderately severe compressive SCI in female Sprague-Dawley rats. Nrg-1 (2 μg/day) or saline was delivered subcutaneously through osmotic mini-pumps starting 30 min after SCI. We conducted flow cytometry, quantitative real-time PCR, and immunohistochemistry at acute, subacute, and chronic stages of SCI to investigate the effects of Nrg-1 treatment on systemic and spinal cord immune response as well as cytokine, chemokine, and antibody production.
Results
We provide novel evidence that Nrg-1 promotes a pro-regenerative immune response after SCI. Bioavailability of Nrg-1 stimulated a regulatory phenotype in T and B cells and augmented the population of M2 macrophages in the spinal cord and blood during the acute and chronic stages of SCI. Importantly, Nrg-1 fostered a more balanced microenvironment in the injured spinal cord by attenuating antibody deposition and expression of pro-inflammatory cytokines and chemokines while upregulating pro-regenerative mediators.