Cofilin-actin rod formation in neuronal processes after brain ischemia.

Abstract

Functional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions. Here we evaluated four mouse models of brain ischemia to define the conditions that drive formation of cofilin-actin rods. Three of the models provide early reperfusion: transient middle cerebral artery occlusion (MCAo), transient bilateral common carotid artery occlusion (CCAo), and cardiac arrest / cardiopulmonary resuscitation (CA/CPR). Early reperfusion restores ATP generating capacity, but also induces oxidative stress. The fourth model, photothrombotic cortical infarction, does not provide reperfusion. Cofilin-actin rods were formed in each of these models, but with differing patterns. Where acute reperfusion occurred, rod formation was maximal within 4 hours after reperfusion. Where infarction occurred, rods continued to form for at least 24 hours after ischemic onset, and extended into the adjacent non-ischemic tissue. Interventions that limit cofilin-actin rod formation may help to preserve integrity of neuronal processes in permanent ischemia.

• Authors: Seok Joon Won, Angela M Minnella, Long Wu, Claire H Eun, Eric Rome, Paco S Herson, Alisa E Shaw, James R Bamburg, Raymond A Swanson
• Journal: PloS one (PLoS One) Vol. 13 Issue 10 Pg. e0198709 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30325927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Actins
• Cofilin 1

Topics

• Actins (analysis, metabolism, ultrastructure)
• Animals
• Brain Ischemia (metabolism, pathology)
• Cells, Cultured
• Cofilin 1 (analysis, metabolism, ultrastructure)
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Neurons (metabolism, pathology)
• Oxidative Stress
• Protein Aggregation, Pathological (metabolism, pathology)