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Ampakines Increase Spinal Respiratory Motor Output after Cervical Spinal Cord Injury in Rats
Author(s) -
Streeter Kristi,
GonzalezRothi Elisa,
Sandhu Milap,
Baekey David,
Greer John,
Fuller David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1299.4
Subject(s) - spinal cord , glutamatergic , medicine , spinal cord injury , anesthesia , respiratory center , neuroscience , respiratory system , neurotransmission , phrenic nerve , ampa receptor , glutamate receptor , psychology , anatomy , receptor
Glutamatergic synaptic transmission is a fundamental component of the neural drive to breathe, and α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) mediated synaptic currents contribute to respiratory rhythmogenesis and respiratory motoneuron depolarization during inspiration. Ampakines are a class of synthetic compounds initially designed to enhance AMPAR‐mediated glutamatergic neurotransmission related to cognition, learning and memory. Ampakines are also a potent respiratory stimulant, particularly during conditions of suppressed respiratory motor output. While ampakines have been safely used in clinical studies, to our knowledge they have never been evaluated with respect to neurological disorders that compromise breathing, such as cervical spinal cord injury (SCI). Therefore, we aimed to test the hypothesis that ampakines increase respiratory motor output following cervical spinal cord injury. To test this hypothesis, we gave ampakine CX717 to urethane anesthetized rats (15–30 mg/kg, i.v.) with chronic (2–8 wks) cervical (C2) hemi‐section injury (C2Hx) or mid‐cervical (C3/C4) lateral contusion injury. In preliminary experiments, ampakines caused a rapid and robust increase in phrenic motor output ipsilateral to the injury and also increased contralateral phrenic motor output to a lesser extent. Responses were similar across time points post‐injury. In addition, we observed that i.v. ampakine caused a rapid change in the discharge of spinal interneurons below the spinal injury in the vicinity of the phrenic motor pool (C4). These initial results indicate that ampakine CX717 can stimulate respiratory motor output following cervical spinal cord injury, and also alters the activity of the mid‐cervical propriospinal network. Support or Funding Information Funding: 1R01NS080180‐01A1 (DF) and 1F32NS095620‐01 (KS)