Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression

Autor: Behzad M. Toosi, Atiq Hassan, Gillian D. Muir, Breanna M. Arnold, Valerie M. K. Verge, Sally Caine
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Nervous system
Male
Vascular Endothelial Growth Factor A
Critical Care and Emergency Medicine
Protein Expression
Immunofluorescence
lcsh:Medicine
Tropomyosin receptor kinase B
Biochemistry
Nervous System
0302 clinical medicine
Neurotrophic factors
Animal Cells
immune system diseases
Medicine and Health Sciences
Gray Matter
Spinal Cord Injury
Hypoxia
lcsh:Science
Spinal cord injury
Trauma Medicine
Neurons
Motor Neurons
Multidisciplinary
Neuronal Plasticity
Lumbar Vertebrae
Intermittent hypoxia
medicine.anatomical_structure
Spinal Cord
Neurology
Acute Disease
Cervical Vertebrae
medicine.symptom
Cellular Types
Anatomy
Traumatic Injury
Research Article
medicine.medical_specialty
Motor Proteins
Nerve Tissue Proteins
Motor Activity
Research and Analysis Methods
Choline O-Acetyltransferase
Lesion
03 medical and health sciences
Molecular Motors
Internal medicine
medicine
Gene Expression and Vector Techniques
Animals
Receptor
trkB
Molecular Biology Techniques
Immunoassays
Molecular Biology
Spinal Cord Injuries
Molecular Biology Assays and Analysis Techniques
business.industry
Brain-Derived Neurotrophic Factor
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
Recovery of Function
Hypoxia (medical)
medicine.disease
Spinal cord
Hypoxia-Inducible Factor 1
alpha Subunit
digestive system diseases
Neuroanatomy
030104 developmental biology
Endocrinology
Rats
Inbred Lew
Cellular Neuroscience
Immunologic Techniques
lcsh:Q
business
Neurotrauma
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS ONE, Vol 13, Iss 5, p e0197486 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: One of the most promising approaches to improve recovery after spinal cord injury (SCI) is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH, brief exposures to reduced O2 levels alternating with normal O2 levels) initiates plasticity in respiratory systems and has been shown to improve recovery in respiratory and non-respiratory spinal systems after SCI in experimental animals and humans. Although the mechanism by which AIH elicits its effects after SCI are not well understood, AIH is known to alter protein expression in spinal neurons in uninjured animals. Here, we examine hypoxia- and plasticity-related protein expression using immunofluorescence in spinal neurons in SCI rats that were treated with AIH combined with motor training, a protocol which has been demonstrated to improve recovery of forelimb function in this lesion model. Specifically, we assessed protein expression in spinal neurons from animals with incomplete cervical SCI which were exposed to AIH treatment + motor training either for 1 or 7 days. AIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 weeks post-SCI. Both 1 or 7 days of AIH treatment + motor training resulted in significantly increased expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) relative to normoxia-treated controls, in neurons both proximal (cervical) and remote (lumbar) to the SCI. All other markers examined were significantly elevated in the 7 day AIH + motor training group only, at both cervical and lumbar levels. These markers included vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and phosphorylated and nonphosphorylated forms of the BDNF receptor tropomyosin-related kinase B (TrkB). In summary, AIH induces plasticity at the cellular level after SCI by altering the expression of major plasticity- and hypoxia-related proteins at spinal regions proximal and remote to the SCI. These changes occur under the same AIH protocol which resulted in recovery of limb function in this animal model. Thus AIH, which induces plasticity in spinal circuitry, could also be an effective therapy to restore motor function after nervous system injury.
Databáze: OpenAIRE
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