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Journal article
Rehabilitation Decreases Spasticity by Restoring Chloride Homeostasis through the Brain-Derived Neurotrophic Factor–KCC2 Pathway after Spinal Cord Injury
Journal of neurotrauma, v 37(6), pp 846-859
06 Mar 2020
PMID: 31578924
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Activity-based therapy is routinely integrated in rehabilitation programs to facilitate functional recovery after spinal cord injury (SCI). Among its beneficial effects is a reduction of hyperreflexia and spasticity, which affects ∼75% of the SCI population. Unlike current anti-spastic pharmacological treatments, rehabilitation attenuates spastic symptoms without causing an active depression in spinal excitability, thus avoiding further interference with motor recovery. Understanding how activity-based therapies contribute to decrease spasticity is critical to identifying new pharmacological targets and to optimize rehabilitation programs. It was recently demonstrated that a decrease in the expression of KCC2, a neuronal Cl
–
extruder, contributes to the development spasticity in SCI rats. Although exercise can decrease spinal hyperexcitability and increase KCC2 expression on lumbar motoneurons after SCI, a causal effect remains to be established.
Activity-dependent processes include an increase in brain-derived neurotrophic factor (BDNF) expression. Interestingly, BDNF is a regulator of KCC2 but also a potent modulator of spinal excitability. Therefore, we hypothesized that after SCI, the activity-dependent increase in KCC2 expression: 1) functionally contributes to reduce hyperreflexia, and 2) is regulated by BDNF. SCI rats chronically received VU0240551 (KCC2 blocker) or TrkB-IgG (BDNF scavenger) during the daily rehabilitation sessions and the frequency-dependent depression of the H-reflex, a monitor of hyperreflexia, was recorded 4 weeks post-injury. Our results suggest that the activity-dependent increase in KCC2 functionally contributes to H-reflex recovery and critically depends on BDNF activity. This study provides a new perspective in understanding how exercise impacts hyperreflexia by identifying the biological basis of the recovery of function.
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Details
- Title
- Rehabilitation Decreases Spasticity by Restoring Chloride Homeostasis through the Brain-Derived Neurotrophic Factor–KCC2 Pathway after Spinal Cord Injury
- Creators
- Henrike Beverungen - Drexel UniversitySamantha Choyke Klaszky - Drexel UniversityMichael Klaszky - Drexel UniversityMarie-Pascale Côté - Drexel University
- Publication Details
- Journal of neurotrauma, v 37(6), pp 846-859
- Publisher
- Mary Ann Liebert, Inc., publishers
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000496153400001
- Scopus ID
- 2-s2.0-85081941623
- Other Identifier
- 991019168867004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences