Structural and functional identification of two distinct inspiratory neuronal populations at the level of the phrenic nucleus in the rat cervical spinal cord

Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator assistance. Thus restoring diaphragm activity and regaining voluntary control of breathing are the primary clinical goals for patients with respiratory dysfunction following cervical SCI. Epidural stimulation (EDS) is a promising strategy that has been explored extensively for nonrespiratory functions and to a limited extent within the respiratory system. The goal of the present study is to assess the potential for EDS at the location of the phrenic nucleus (C3–C5) innervating the diaphragm: the main inspiratory muscle following complete C1 cervical transection. To avoid the suppressive effect of anesthesia, all experiments were performed in decerebrate, C1 cervical transection, unanesthetized, nonparalyzed ( n = 13) and paralyzed ( n = 7) animals. Our results show that C4 segment was the most responsive to EDS and required the lowest threshold of current intensity, affecting tracheal pressure and phrenic nerve responses. High-frequency (200–300 Hz) EDS applied over C4 segment (C4-EDS) was able to maintain breathing with normal end-tidal CO2 level and raise blood pressure. In addition, 100–300 Hz of C4-EDS showed time- and frequency-dependent changes (short-term facilitation) of evoked phrenic nerve responses that may serve as a target mechanism for pacing of phrenic motor circuits. The present work provides the first report of successful EDS at the level of phrenic nucleus in a complete SCI animal model and offers insight into the potential therapeutic application in patients with high cervical SCI. NEW & NOTEWORTHY The present work offers the first demonstration of successful life-supporting breathing paced by epidural stimulation (EDS) at the level of the phrenic nucleus, following a complete spinal cord injury in unanesthetized, decerebrate rats. Moreover, our experiments showed time- and frequency-dependent changes of evoked phrenic nerve activity during EDS that may serve as a target mechanism for pacing spinal phrenic motor networks.

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The Superimposed Effects of Chronic Phrenicotomy and Cervical Spinal Cord Hemisection on Glial Cytoarchitecture in the Rat Phrenic Nucleus

Journal of Spinal Cord Medicine ◽

10.1080/10790268.1996.11719419 ◽

1996 ◽

Vol 19 (2) ◽

pp. 58-70 ◽

Cited By ~ 10

Author(s):

Wayne W. Liou ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Cervical Spinal Cord ◽

Phrenic Nucleus ◽

Spinal Cord Hemisection

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Sequence of activation of neuronal populations in the cat cervical spinal cord by reticulo-, vestibulo-, and rubrospinal influences

Neurophysiology ◽

10.1007/bf01073506 ◽

1980 ◽

Vol 11 (3) ◽

pp. 194-196

Author(s):

N. I. Gaidai

Keyword(s):

Spinal Cord ◽

Cervical Spinal Cord ◽

Neuronal Populations

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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