title: Spinal cord injury in neonates alters respiratory motor output via supraspinal mechanisms.
abstract: Upper cervical spinal cord injury (SCI) alters respiratory output and results in a blunted respiratory response to pH/CO2. Many SCI studies have concentrated on respiratory changes in neural function caudal to injury; however few have examined whether neural plasticity occurs rostral to SCI. Golder et al. (2001a) showed that supraspinal changes occur to alter respiratory output after SCI. Furthermore, Brown et al. (2004) showed that neural receptors change rostral to a thoracic SCI. We hypothesized that SCI in neonates will alter supraspinal output, show a blunted response to pH and alter receptor protein levels in the medulla. On postnatal day 0/1, a C2 SCI surgery was performed. Two days later, neonates were anesthetized and brainstem-spinal cords removed. Respiratory-related activity was recorded using the in vitro brainstem-spinal cord preparation and the superfusate pH was changed (pH 7.2, 7.4 and 7.8). The respiratory-like frequency was significantly reduced in SCI rats indicating supraspinal plasticity. Increasing the pH decreased respiratory-like frequency and peak amplitude in injured and sham controls. Increasing the pH increased burst duration and area in sham controls, whereas in injured rats, the burst duration and area decreased. Western blot analysis demonstrated significant changes in glutamate receptor subunits (NR1, NR2B and GluR2), adenosine receptors (A1, A2A), glutamic acid decarboxylase (65) and neurokinin-1 receptors in medullary tissue ipsilateral and contralateral to injury. These data show that supraspinal plasticity in the respiratory system occurs after SCI in neonate rats. The mechanisms remain unknown, but may involve alterations in receptor proteins involved in neurotransmission.
authors.affiliation: Wayne State University, Department of Anatomy and Cell Biology, Detroit, MI 48201, USA. mzimmer@med.wayne.edu
authors.forename: M Beth
authors.initials: MB
authors.lastname: Zimmer
authors.forename: Harry G
authors.initials: HG
authors.lastname: Goshgarian
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015536:Down-Regulation / Q000502:physiology; D004525:Efferent Pathways / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D008526:Medulla Oblongata / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012125:Respiratory Center / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*; D012131:Respiratory Insufficiency / Q000209:etiology* / Q000503:physiopathology*; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D007527:Isoenzymes; D017470:Receptors, Glutamate; D018040:Receptors, Neurokinin-1; D018047:Receptors, Purinergic P1; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2