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Evaluation of the Nrf2‐mediated anti‐oxidative and anti‐inflammatory responses in phrenic motoneurons following C2 hemisection in adult rat
Author(s) -
Deramaudt T,
Vinit S,
Efthimiadi L,
Keomani E,
Petitjean M,
Bonay M
Publication year - 2015
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.29.1_supplement.656.3
Subject(s) - phrenic nerve , spinal cord injury , spinal cord , medicine , cholera toxin , oxidative stress , inflammation , diaphragm (acoustics) , respiratory system , paralysis , anesthesia , oxidative phosphorylation , pharmacology , chemistry , surgery , biochemistry , physics , psychiatry , acoustics , loudspeaker
The consequences of high cervical spinal cord injuries are permanent respiratory deficits and deleterious inflammatory and oxidative reactions, which may prevent any spontaneous functional recovery. Our laboratory has successfully mastered a preclinical model of respiratory insufficiency consisting in a C2 partial injury which leads to unilateral phrenic and diaphragm paralysis in the adult rat. This injury induces a gradual microglial activation and a macrophage infiltration around the deafferented phrenic motoneurons, identified by Cholera Toxin B‐fragment back‐labeling, hours to days post‐injury. iNOS and C/EBP δ protein levels, two transcriptional factors involved in pro‐inflammatory response, were increased overtime within the phrenic motoneurons. Interestingly, the injury induced a transient reduction in Nrf2 (Nuclear Factor E2‐Related Factor 2) protein, a key regulator in the anti‐inflammatory and anti‐oxidative responses, in the phrenic motoneurons, that was restored to control level at 7 days post‐injury. Our results show that the C2 injury negatively modulates the Nrf2 and the protective mechanisms within the phrenic motoneurons and their vicinity. This suggests a potential therapeutic role of Nrf2 in ameliorating the functional recovery of phrenic motoneurons by reducing the inflammatory and oxidative damages following spinal cord injury.