BDNF effects on functional recovery across motor behaviors after cervical spinal cord injury.
Unilateral C2cervical spinal cord hemisection (SH) disrupts descending excitatory drive to phrenic motor neurons, thereby paralyzing the ipsilateral diaphragm muscle (DIAm) during ventilatory behaviors. Recovery of rhythmic DIAm activity ipsilateral to injury occurs over time, consistent with neuroplasticity and strengthening of spared synaptic inputs to phrenic motor neurons. Localized intrathecal delivery of brain-derived neurotrophic factor (BDNF) to phrenic motor neurons after SH enhances recovery of eupneic DIAm activity. However, the impact of SH and BDNF treatment on the full range of DIAm motor behaviors has not been fully characterized. We hypothesized that all DIAm motor behaviors are affected by SH and that intrathecal BDNF enhances the recovery of both ventilatory and higher force, nonventilatory motor behaviors. An intrathecal catheter was placed in adult, male Sprague-Dawley rats at C4to chronically infuse artificial cerebrospinal fluid (aCSF) or BDNF. DIAm electromyography (EMG) electrodes were implanted bilaterally to record activity across motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2and 5% CO2), sighs, airway occlusion, and sneezing. After SH, ipsilateral DIAm EMG activity was evident in only 43% of aCSF-treated rats during eupnea, and activity was restored in all rats after BDNF treatment. The amplitude of DIAm EMG (root mean square, RMS) was reduced following SH during eupnea and hypoxia-hypercapnia in aCSF-treated rats, and BDNF treatment promoted recovery in both conditions. The amplitude of DIAm RMS EMG during sighs, airway occlusion, and sneezing was not affected by SH or BDNF treatment. We conclude that the effects of SH and BDNF treatment on DIAm activity depend on motor behavior.



This study demonstrates that after unilateral C2spinal cord hemisection (SH), there are differences in the spontaneous recovery of diaphragm (DIAm) electromyographic activity during ventilatory compared with more forceful, nonventilatory motor behaviors. Furthermore, we show that intrathecal delivery of brain-derived neurotrophic factor (BDNF) at the level of the phrenic motor neuron pool enhances recovery of ipsilateral DIAm activity following SH, exerting main effects on recovery of ventilatory but not higher force, nonventilatory behaviors.
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.|Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Vivian
V
Hernandez-Torres
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.|Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Heather M
HM
Gransee
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.|Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Carlos B
CB
Mantilla
Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Yao
Y
Wang
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.
Wen-Zhi
WZ
Zhan
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and sieck.gary@mayo.edu.|Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Gary C
GC
Sieck
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004576:Electromyography; D007839:Functional Laterality / Q000187:drug effects; D001239:Inhalation / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor
motor unit recruitment; neurotrophin; respiration; respiratory muscle; spinal cord injury; spinal hemisection