# Ischemia-induced injury to neuronal processes: role of cofilin-actin rod formation

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2023 · —

## Abstract

Disability caused by ischemic stroke results not only from neuronal death, but also from injury to axons
and dendrites of surviving neurons. The mechanisms by which ischemia causes injury to these neuronal
processes are not well understood, and have not been well-explored as a therapeutic target. Cofilin-actin
rods are 1:1 linear aggregates of cofilin-1 and actin that form in neuronal processes under conditions of
ATP depletion or oxidant stress. These rods cause degeneration of the neuronal processes in which they
persist. Recent studies demonstrate that cofilin-actin rods form in neurons during and after brain
ischemia, and that their formation can be suppressed genetically and pharmacologically. Here we will
determine the extent to which suppression of rod formation (or accelerated rod dissolution) can promote
neurite survival and improve motor function after stroke. We will use transient and permanent models of
stroke in the mouse to evaluate effects of rod suppression on survival of neuronal processes at specified
intervals after ischemia. We will evaluate the effects of rod suppression on motor impairment and
recovery using a skilled reaching task and other measures of forelimb dexterity. We also aim to better
elucidate the role of inflammation and subcellular mechanisms that drive rod formation and link rod
formation to subsequent neurite degeneration. We will employ subcellular fluorescent probes and real-
time imaging in cell culture preparations to determine why rods form and persist in specific locations of
neurons, and do so even after the ischemic stimuli are removed; whether the persistence of cofilin-actin
rods represent stable aggregates; and whether rod formation influences bioenergetic failure in the
affected neurites.

## Key facts

- **NIH application ID:** 10664943
- **Project number:** 5I01BX004884-04
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** RAYMOND A SWANSON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10664943

## Citation

> US National Institutes of Health, RePORTER application 10664943, Ischemia-induced injury to neuronal processes: role of cofilin-actin rod formation (5I01BX004884-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10664943. Licensed CC0.

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