ArticleFrontiers in cellular neuroscience2014
Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Big conductance calcium-activated potassium channel openers control spasticity without sedation.British journal of pharmacology · 2017Trial
- Compensatory scaling of modulatory neural populations in response to motor challenges.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Review
- Multi-path direct current spinal stimulation extended survival in the SOD1-G93A model of amyotrophic lateral sclerosis.Frontiers in neurology · 2025Article
- VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons.International journal of molecular sciences · 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
- Excitatory to inhibitory synaptic ratios are unchanged at presymptomatic stages in multiple models of ALS.PloS one · 2024Article
- The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence.Cellular and molecular neurobiology · 2023Review
- KCC2 downregulation after sciatic nerve injury enhances motor function recovery.Scientific reports · 2023Article
- Article
- Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.Cells · 2022Review
- Rate-dependent depression is impaired in amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- Chloride Homeostasis in Developing Motoneurons.Advances in neurobiology · 2022Article
- Locomotor deficits induced by lumbar muscle inflammation involve spinal microglia and are independent of KCC2 expression in a mouse model of complete spinal transection.Experimental neurology · 2021Article
- Absence of Subcerebral Projection Neurons Is Beneficial in a Mouse Model of Amyotrophic Lateral Sclerosis.Annals of neurology · 2020Article
- Therapeutic Role of Neuregulin 1 Type III in SOD1-Linked Amyotrophic Lateral Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Rehabilitation Decreases Spasticity by Restoring Chloride Homeostasis through the Brain-Derived Neurotrophic Factor-KCC2 Pathway after Spinal Cord Injury.Journal of neurotrauma · 2020Article
- Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity.eLife · 2019Article
- Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury.The Journal of physiology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease manifested by progressive muscle atrophy and paralysis due to the loss of upper and lower motoneurons (MN). Spasticity appears in ALS patients leading to further disabling consequences. Loss of the inhibitory tone induced by downregulation of the potassium chloride cotransporter 2 (KCC2) in MN has been proposed to importantly contribute to the spastic behavior after spinal cord injury (SCI). The aim of the present study was to test whether the alterations in the expression of KCC2 are linked to the appearance of spasticity in the SOD(G93A) ALS murine model. We compared SOD(G93A) mice to wild type mice subjected to SCI to mimic the spinal MN disconnection from motor descending pathways, and to sciatic nerve lesion to mimic the loss of MN connectivity to muscle. Electrophysiological results show that loss of motor function is observed at presymptomatic stage (8 weeks) in SOD(G93A) mice but hyperreflexia and spasticity do not appear until a late stage (16 weeks). However, KCC2 was not downregulated despite MN suffered disconnection both from muscles and upper MNs. Further experiments revealed decreased gephyrin expression, as a general marker of inhibitory systems, accompanied by a reduction in the number of Renshaw interneurons. Moreover, 5-HT fibers were increased in the ventral horn of the lumbar spinal cord at late stage of disease progression in SOD1(G93A) mice. Taken together, the present results indicate that spasticity appears late in the ALS model, and may be mediated by a decrease in inhibitory interneurons and an increase of 5-HT transmission, while the absence of down-regulation of KCC2 could rather indicate an inability of MNs to respond to insults.
Indexed as
Identifiers
What OpenQuestion holds
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.