Exercise Modulates Chloride Homeostasis after Spinal Cord Injury

The Journal of Neuroscience, 2014 · DOI: 10.1523/JNEUROSCI.0678-14.2014 · Published: July 2, 2014

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

Activity-based therapies, including exercise, are commonly used in spinal cord injury (SCI) rehabilitation to reduce hyperreflexia and spasticity. However, how exercise achieves these benefits is not well understood. Following SCI, there are persisting alterations in how GABA, a neurotransmitter, acts on nerve cells. The effectiveness of GABA depends on chloride concentration inside the cells, which is controlled by proteins called KCC2 and NKCC1. This study found that exercise after SCI helps restore the normal balance of chloride levels by increasing KCC2 and decreasing NKCC1, which improves reflex recovery. This suggests targeting these proteins could enhance rehabilitation outcomes.

Study Duration

7, 14, 28, or 56 days

Participants

87 adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord after SCI.
2
Blocking KCC2 with DIOA masked the effect of exercise on low-frequency-dependent depression (FDD), while blocking NKCC1 with bumetanide restored FDD toward intact levels.
3
Exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI.

Research Summary

This study investigates the role of exercise in modulating chloride homeostasis after spinal cord injury (SCI) and its impact on reflex recovery. The findings indicate that exercise restores spinal excitability and normalizes levels of KCC2 and NKCC1, key chloride cotransporters, in the lumbar spinal cord. Pharmacological manipulation of KCC2 and NKCC1 further supports the role of chloride homeostasis in reflex recovery, suggesting potential therapeutic targets for improving functional recovery after SCI.

Practical Implications

Therapeutic Target Identification

Chloride cotransporters (CCCs) may serve as potential therapeutic targets to improve functional recovery when combined with rehabilitation programs.

Rehabilitation Strategy Enhancement

Exercise-based therapies can be optimized to promote chloride homeostasis and improve reflex recovery after SCI.

Pharmacological Adjuncts

Combining exercise with pharmacological interventions targeting KCC2 and NKCC1 could potentially enhance rehabilitation outcomes.

Study Limitations

1
The study was conducted on rats, and results may not directly translate to humans.
2
The specific mechanisms by which exercise modulates KCC2 and NKCC1 expression require further investigation.
3
The long-term effects of exercise on chloride homeostasis and functional recovery after SCI were not examined.

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