Related Experiment Video
Updated: Aug 18, 2026
An Ex Vivo Laser-induced Spinal Cord Injury Model to Assess Mechanisms of Axonal Degeneration in Real-time
Published on: November 25, 2014
Ionic mechanisms of aglycemic axon injury in mammalian central white matter
A M Brown1, R Wender, B R Ransom
1Department of Neurology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Abstract:
The authors investigated ionic mechanisms underlying aglycemic axon injury in adult rat optic nerve, a central white matter tract. Axon function was assessed using evoked compound action potentials (CAPs). Glucose withdrawal led to delayed CAP failure, an alkaline extracellular pH shift, and an increase in extracellular [K(+)]. Sixty minutes of glucose withdrawal led to irreversible axon injury. Aglycemic axon injury required extracellular calcium; the extent of injury progressively declined as bath [Ca(2+)] was decreased. To evaluate Ca(2+) movements during aglycemia, the authors recorded extracellular [Ca(2+)] ([Ca(2+)](o)) using Ca(2+)-sensitive microelectrodes. Under control conditions, [Ca(2+)](o) fell with a similar time course to CAP failure, indicating extracellular Ca(2+) moved to an intracellular position during aglycemia. The authors quantified the magnitude of [Ca(2+)]o decrease as the area below baseline [Ca(2+)]o during aglycemia and used this as a qualitative measure of Ca(2+) influx. The authors studied the mechanisms of Ca(2+) influx. Blockade of Na(+) influx reduced Ca(2+) influx and improved CAP recovery, suggesting Na(+)-Ca(2+) exchanger involvement. Consistent with this hypothesis, bepridil reduced axon injury. In addition, diltiazem or nifedipine decreased Ca(2+) influx and increased CAP recovery. The authors conclude aglycemic central white matter injury is caused by Ca(2+) influx into intracellular compartments through reverse Na(+)-Ca(2+) exchange and L-type Ca(2+) channels.
Insights
Aglycemic axon injury in rat optic nerves involves calcium influx. Blocking sodium-calcium exchangers and L-type calcium channels protects axons from glucose withdrawal damage.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Aglycemia, or glucose deprivation, causes central white matter axon injury.
- Axon function is typically assessed using evoked compound action potentials (CAPs).
- Extracellular ion shifts, including pH and potassium, accompany aglycemic conditions.
Purpose of the Study:
- To investigate the ionic mechanisms behind aglycemic axon injury in the adult rat optic nerve.
- To determine the role of calcium influx in aglycemic central white matter damage.
- To identify specific channels and transporters involved in calcium entry during glucose withdrawal.
Main Methods:
- Measuring evoked compound action potentials (CAPs) to assess axon function.
- Monitoring extracellular pH and potassium concentrations.
- Utilizing calcium-sensitive microelectrodes to record extracellular calcium ([Ca(2+)](o)) changes.
- Employing pharmacological agents to block specific ion channels and exchangers (e.g., Na(+)-Ca(2+) exchanger, L-type Ca(2+) channels).
Main Results:
- Glucose withdrawal induced delayed CAP failure, extracellular alkalosis, and increased extracellular potassium.
- Aglycemic axon injury was dependent on extracellular calcium, with reduced injury at lower [Ca(2+)].
- A decrease in [Ca(2+)](o) during aglycemia indicated calcium influx into cells.
- Blockade of Na(+) influx, reverse Na(+)-Ca(2+) exchange (using bepridil), and L-type Ca(2+) channels (using diltiazem or nifedipine) reduced calcium influx and improved CAP recovery.
Conclusions:
- Aglycemic central white matter injury is mediated by calcium influx.
- Reverse Na(+)-Ca(2+) exchange and L-type Ca(2+) channels are key pathways for calcium entry during aglycemia.
- Targeting these pathways may offer therapeutic strategies for central white matter injury.
Related Concept Videos
01:15Neurogenesis and Regeneration of Nervous Tissue
01:25Secondary Spinal Cord Injury llI: Pathophysiology