# Astrocyte regulation of neural plasticity after CNS injury

> **NIH NIH R00** · CEDARS-SINAI MEDICAL CENTER · 2020 · $245,477

## Abstract

Spinal cord injury (SCI) is a devastating neurologic insult that can disrupt ascending and descending
neural circuits necessary for walking, somatosensation, urination and other vital autonomic functions. The
majority of SCI patients suffer from anatomically and functionally incomplete spinal cord injury (I-SCI) that
results in varying degrees of neurological dysfunction. Although long-distance regeneration of central nervous
system (CNS) axons does not occur in mammals, clinical and experimental studies demonstrate considerable
spontaneous recovery of neurological function after I-SCI. Experimental studies in rodents and non-human
primates indicate that synaptic reorganization between supraspinal motor tracts and spared intraspinal relay
circuits that bypass a spinal lesion can re-establish brain-cord communication, and give rise to remarkable
motor recovery after I-SCI. Unfortunately, a limited understanding of the cellular and molecular mechanisms
governing this functionally meaningful intraspinal circuit plasticity has precluded development of therapeutics to
augment this spontaneously occurring recovery process. Astrocytes are critical regulators of synaptogenesis
and circuit development during development, and moderate synaptic strength and structural synaptic plasticity
following changes in neural activity. In response to diverse CNS injuries, astrocytes undergo graded and
regionally distinct changes in structure and function collectively referred to as reactive astrogliosis. After SCI,
scar-forming, reactive astrocytes surrounding lesions are indispensible regulators of inflammation. The
functions of non-scar-forming, reactive perineuronal astrocytes in spinal cord regions undergoing functionally
meaningful circuit remodeling after SCI are not clear, but potential roles include regulation of synapse recovery
and neuroprotection. The objective of the current study is to delineate fundamental molecular mechanisms
through which astrocytes modulate intraspinal synaptic reorganization and spontaneous locomotor recovery
after SCI. This research will test the overriding hypothesis that after I-SCI, intraspinal perineuronal astrocytes
in spared tissue undergo changes in transcriptional profile that modulate and promote intraspinal synaptic
plasticity and circuit remodeling underlying spontaneous locomotor recovery. In Aim 1, I will use astrocyte-specific
transcriptomics to delineate changes in perineuronal astrocyte gene expression that underlie
supraspinal-intraspinal synaptic plasticity within key spinal circuit reorganizing zones rostral to an I-SCI lesion.
In Aim 2, I will assess the relevance of perineuronal astrocyte reactivity for supraspinal-intraspinal synaptic
remodeling and motor recovery. In Aim 3, I will compare mechanisms through which astrocytes regulate
supraspinal-intraspinal plasticity in reorganizing zones above an I-SCI lesion, with those regulating
sensorimotor circuit reorganization within the denervated motor centers below....

## Key facts

- **NIH application ID:** 10004175
- **Project number:** 5R00NS105915-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Joshua Evan Burda
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,477
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004175

## Citation

> US National Institutes of Health, RePORTER application 10004175, Astrocyte regulation of neural plasticity after CNS injury (5R00NS105915-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004175. Licensed CC0.

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