# Spreading Depolarizations and Perfusion in Non-traumatic Spinal Cord Injury

> **NIH VA I21** · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · 2022 · —

## Abstract

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord damage in older adults. It is
characterized by physical compression of the spinal cord and often progresses gradually over months to years,
manifesting as weakness, numbness, and pain. Because it is a disease that disproportionately affects an aging
population and leads to decreased quality of life, it has a high relevance to Veterans. Many patients with CSM
have favorable outcomes after surgical intervention, but opportunities to improve outcomes through mechanistic
understanding of the disease process and improved diagnostic markers would be beneficial to improve diagnosis
and patient management, potentially leading to improvements in therapies. This project aims to examine the role
of spreading depolarization and perfusion deficits in the context of CSM in preclinical animal models. Spreading
depolarization (SD) is an abnormal wave of ionic and electrical that propagates through central nervous system
tissues after an insult. While SDs have been well-established and characterized after acute physical trauma,
they have not been investigated with persistent or repetitive physical compression of the spinal cord that is the
hallmark of CSM. Further, SDs and underlying perfusion deficits are tightly coupled. Neurons with sufficient
oxygen and glucose can recover from SDs, but neurons that are lack sufficient metabolic substrates have a high
likelihood of being irreparably damaged by SDs. This project will use an animal model and electrophysiological
recordings to characterize SD events in the spinal cord in the context of continuous or dynamic physical
compression (Aim 1). In parallel, it will examine the perfusion deficits in the spinal cord using MRI or intraspinal
pressure sensors in the context of a clinically relevant animal model of CSM with progressive spinal cord
compression (Aim 2). Collectively, these studies will elucidate the mechanisms of spinal cord damage in CSM
and may provide new avenues for diagnostic markers. Detecting abnormal perfusion noninvasively with MRI has
a clear translational path for subsequent clinical studies of CSM patients. The team of investigators on this project
have individual expertise in all of the different subject areas, and their combined multi-disciplinary approach to
these studies will collectively examine a new research area with potential high clinical relevance and translational
opportunities.

## Key facts

- **NIH application ID:** 10480464
- **Project number:** 1I21RX003857-01A1
- **Recipient organization:** CLEMENT J. ZABLOCKI VA MEDICAL CENTER
- **Principal Investigator:** MATTHEW D BUDDE
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480464

## Citation

> US National Institutes of Health, RePORTER application 10480464, Spreading Depolarizations and Perfusion in Non-traumatic Spinal Cord Injury (1I21RX003857-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10480464. Licensed CC0.

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