Spinal plasticity following intermittent hypoxia: implications for spinal injury.
Plasticity is a fundamental property of the neural system controlling breathing. One frequently studied model of respiratory plasticity is long-term facilitation of phrenic motor output (pLTF) following acute intermittent hypoxia (AIH). pLTF arises from spinal plasticity, increasing respiratory motor output through a mechanism that requires new synthesis of brain-derived neurotrophic factor, activation of its high-affinity receptor, tropomyosin-related kinase B, and extracellular-related kinase mitogen-activated protein kinase signaling in or near phrenic motor neurons. Because intermittent hypoxia induces spinal plasticity, we are exploring the potential to harness repetitive AIH as a means of inducing functional recovery in conditions causing respiratory insufficiency, such as cervical spinal injury. Because repetitive AIH induces phenotypic plasticity in respiratory motor neurons, it may restore respiratory motor function in patients with incomplete spinal injury.
Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin, USA.
Erica A
EA
Dale-Nagle
Michael S
MS
Hoffman
Peter M
PM
MacFarlane
Irawan
I
Satriotomo
Mary Rachael
MR
Lovett-Barr
Stéphane
S
Vinit
Gordon S
GS
Mitchell
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002574:Cervical Vertebrae / Q000293:injuries; D004789:Enzyme Activation; D006801:Humans; D006973:Hypertension / Q000209:etiology; D000860:Hypoxia / Q000503:physiopathology*; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology / Q000503:physiopathology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012893:Sleep Wake Disorders / Q000209:etiology / Q000503:physiopathology; D013116:Spinal Cord / Q000502:physiology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; D044348:Receptors, Serotonin, 5-HT2; D011493:Protein Kinase C