# Maladaptive Plasticity in Spinal Cord Injury: Cellular Mechanisms

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $610,222

## Abstract

PROJECT SUMMARY/ABSTRACT
Spinal cord Injury (SCI) produces a devastating syndrome characterized by motor dysfunction, hyper-reflexia,
spasticity, and neurogenic pain. The long-term goal of SCI therapy is to promote adaptive plasticity for
restoration of function while limiting maladaptive plasticity that results in hyper-reflexia, spasticity and
intractable pain. Recent research has indicated that both adaptive and maladaptive CNS plasticity can occur at
the level of the spinal cord to dictate recovery of function. However, the specific conditions that promote
adaptive versus maladaptive spinal plasticity in SCI are not well-understood. The central hypothesis of this
R01 is that spinal cord plasticity is shaped by aberrant peripheral stimulation in the acute phase of SCI that tips
plasticity toward a maladaptive form. This hypothesis has strong clinical/translational relevance, as
epidemiological studies indicate that peripheral injuries and early limb disuse are prevalent comorbidities in
human SCI. Up to 85% of SCI individuals presenting to level I trauma centers have peripheral injuries in
addition to CNS damage. Preliminary data demonstrate that peripheral nociceptive stimulation delivered
caudal to a complete SCI lesion produces maladaptive spinal plasticity that manifests as tactile hyper-reflexia
and spasticity. Similar effects are observed with peripheral nerve injury or forced hindlimb disuse below SCI,
and in both transection SCI and contusion SCI models. Our findings link these effects to specific alterations in
glutamate receptor-mediated synaptic plasticity in the spinal ventral horn, providing a novel therapeutic target
for restoration of function after SCI. The Aims of this R01 expand on the preliminary data to: 1) test
mechanistic underpinnings of aberrant nociceptive stimulation below SCI (Aim 1), 2) evaluate whether similar
effects occur with aberrant proprioceptive stimulation driving spinal cord central neuronal hyper-
reflexia/spasticity (Aim 2), and 3) test new targets for combating maladaptive plasticity to promote adaptive
recovery in SCI using transcriptomic and transgenic technologies (Aim 3). The proposed project has
implications for shaping acute neuronal activity in polytraumatic SCI—a prevalent clinical presentation where
CNS lesions are accompanied with peripheral injuries and protracted bedrest.

## Key facts

- **NIH application ID:** 10449363
- **Project number:** 5R01NS122888-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ADAM R FERGUSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $610,222
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449363

## Citation

> US National Institutes of Health, RePORTER application 10449363, Maladaptive Plasticity in Spinal Cord Injury: Cellular Mechanisms (5R01NS122888-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10449363. Licensed CC0.

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