Elucidating the innate immune response and its affect on glial bridging after spinal cord injury in zebrafish

NIH RePORTER · NIH · P20 · $208,058 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Approximately 290,000 Americans live with spinal cord injury (SCI) representing a burden to health-care systems and economies. A better understand of the process of SCI and new therapeutic strategies are needed to tackle this significant problem. There is no effective cure for SCIs often leading to a lifetime of therapy and permanent disability. Regenerative species that can overcome the deleterious effects of SCI are a great resource to identify new therapeutic targets. The zebrafish shares many organizational, cellular and molecular pathways with mammals; however, regeneration and locomotor recovery occurs even after complete transection of the spinal cord. In contrast to mammals, immune cells are differently recruited to the site of injury in zebrafish and inflammation resolves. Little is known about (1) why immune cell recruitment is different, (2) what dictates resolution of the inflammatory phase in zebrafish and (3) whether resolution of inflammation contributes to promotion of a glial bridging instead of the glial scarring seen with mammals. In this proposal, we will investigate the role electrical signaling plays in recruitment and resolution of immune cells and whether changes in the electrical network promotes glial bridging. The results of the proposed experiments will clarify the relationship between electrical signaling, immune cell resolution, and glial bridging and advance our ability to identify new therapeutic approaches to attenuate inflammation and promote recovery.

Key facts

NIH application ID
10495799
Project number
2P20GM121310-06
Recipient
UNIVERSITY OF WYOMING
Principal Investigator
Karen Mruk
Activity code
P20
Funding institute
NIH
Fiscal year
2022
Award amount
$208,058
Award type
2
Project period
2017-09-01 → 2027-07-31