ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Exercise modulates chloride homeostasis after spinal cord injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Mechanisms of exercise-based rehabilitation following intracerebral hemorrhage: insights from preclinical evidence.Frontiers in pharmacology · 2026Pooled it
- Repeated transspinal stimulation decreases soleus H-reflex excitability and restores spinal inhibition in human spinal cord injury.PloS one · 2019Trial
- Modulating the WNK1-SPAK/OSR1-KCC2 Pathway: Acupuncture's Therapeutic Potential in Mitigating Muscle Hypertonia in Ischemic Stroke Rats.Neurochemical research · 2026Article
- Molecular pathways linking traumatic brain injury to cardiovascular dysfunction: therapeutic potential of physical exercise.Metabolic brain disease · 2026Review
- Reduced Post-Activation Depression in Humans with Spinal Cord Injury Is Not Related to Stretch Reflex Hyperexcitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Recovery in gait and posture: a network-based approach to the assessment of rehabilitation effectiveness after spinal cord injury.Frontiers in network physiology · 2026Article
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Electroactive biomaterials modulating ion channels in nervous system regeneration.Regenerative biomaterials · 2026Review
- KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury.The Journal of physiology · 2025Article
- Review
- Transcutaneous Spinal Stimulation Modulates Spinal Reflex Circuit Excitability in Persons with Spinal Cord Injury.Biomedicines · 2025Article
- Transcutaneous spinal cord stimulation at alternating intensities preferentially prevents the development of spasticity after contusion SCI in rat.The Journal of physiology · 2025Article
- The Role of Ion-Transporting Proteins on Crosstalk Between the Skeletal Muscle and Central Nervous Systems Elicited by Physical Exercise.Molecular neurobiology · 2025Review
- Brief early-life motor training induces behavioral changes and alters neuromuscular development in mice.PLoS biology · 2025Article
- Multi-session transcutaneous spinal cord stimulation prevents chloride homeostasis imbalance and the development of hyperreflexia after spinal cord injury in rat.Experimental neurology · 2024Article
- Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Ion Channel Dysregulation Following Intracerebral Hemorrhage.Neuroscience bulletin · 2024Review
- Updating perspectives on spinal cord function: motor coordination, timing, relational processing, and memory below the brain.Frontiers in systems neuroscience · 2024Review
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- Bridging the gap: a translational perspective in spinal cord injury.Experimental biology and medicine (Maywood, N.J.) · 2024Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.