# Astrocyte dynamics in spinal cord injury and their impact on regeneration

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2024 · $76,828

## Abstract

Project Summary
The ability to heal from injuries is fundamental to survival and each body system has mechanisms built into its
physiology to mitigate injuries and promote healing. In the central nervous system (CNS), astrocytes play a
pivotal role in mitigating damage and promoting healing upon injury. Astrocytes undergo significant
physiological changes following injury, straying from their many homeostatic functions in favor of injury directed
roles. In the human CNS, the process of healing involves formation of a glial scar which is necessary for initial
wound healing, but its persistence in the long-term has negative impacts on regenerative capacity leading to
permanent disability. This is thought in large part to be due to the changes that occur in astrocytes following
injury, however, the precise role of astrocytes in regeneration remains elusive, due in part to the heterogeneity
in responses of astrocytes to different types of injury. Many genetic and molecular factors have been identified
in the literature to be differentially regulated in astrocytes, but for many the causal relationship between
astrocyte expression and their impact on regeneration remains elusive. Elucidating the direct astrocyte-neuron
interactions that occur following injury and during regeneration represents the next frontier necessary to
understand the cellular and molecular processes that promote functional regeneration in the CNS.
Unlike most mammals, several other vertebrate species, including zebrafish used in this proposal, are capable
of robust spontaneous regeneration and functional recovery even after severe CNS injuries. I hypothesize that
astrocytes participate in the injury response in the zebrafish CNS and contribute to regeneration. Aim 1 of this
proposal will define the dynamic behavior of astrocytes induced by neuronal injury in vivo. I will use
advanced imaging approaches combined with molecular analysis and genetic manipulations to identify
conserved astrocyte behaviors in a regeneration-capable model and identify those behaviors that promote
regeneration. Aim 2 will address the molecular pathways that regulate astrocyte response to injury and
their impact on regeneration by investigating the role of the conserved gene leucine rich repeat
containing 15 (lrrc15). Mammalian homologues of lrrc15 have been shown to be upregulated in astrocytes
around debris in the diseased brain, but its involvement in injury and regeneration has not been investigated.
My preliminary data indicates that loss of lrrc15 negatively impacts axon regeneration in the spinal cord and
this proposal will identify the specific role lrrc15 plays in astrocytes during injury and regeneration. I will use
expression analysis and cell-specific rescue experiments to determine when and where Lrrc15 acts to promote
regeneration. Together, this proposal will employ a variety of genetic and imaging approaches to identify the
cellular and molecular processes used by astrocytes to promote fun...

## Key facts

- **NIH application ID:** 10901468
- **Project number:** 1F32HD115421-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Alexandria Lassetter Hulegaard
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,828
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901468

## Citation

> US National Institutes of Health, RePORTER application 10901468, Astrocyte dynamics in spinal cord injury and their impact on regeneration (1F32HD115421-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10901468. Licensed CC0.

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