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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/29536

Title: Stress Pathway Modulation Is Detrimental or Ineffective for Functional Recovery after Spinal Cord Injury in Mice
Authors: Lemmens, Stefanie
Nelissen, Sofie
Dooley, Dearbhaile
Geurts, Nathalie
Peters, Eva Milena Johanne
Hendrix, Sven
Issue Date: 2019
Publisher: MARY ANN LIEBERT, INC
Citation: JOURNAL OF NEUROTRAUMA,
Status: Early View
Abstract: A mounting body of evidence suggests that stress plays a major role in the injury progression after spinal cord injury (SCI). Injury activates the stress systems; this in turn may augment the generation of pro-inflammatory cytokines, stimulate pro-inflammatory immune cells, and alter the balance between the pro- and anti-inflammatory immune response. As a result, it is suggested that stress pathways may augment neuronal damage and loss after SCI. Considering these potential detrimental effects of stress after SCI, we hypothesized that inhibition of stress pathways immediately after SCI may offer protection from damage and improve recovery. To investigate the relevance of stress responses in SCI recovery, we investigated the effects of blocking three well-studied stress response axes in a mouse model of SCI. Propranolol, RU-486, and CP-99994 were administered to inhibit the sympathetic axis, the hypothalamus-pituitary-adrenal axis, and the neuropeptide axis, respectively. Surprisingly, assessing functional recovery by the Basso Mouse Scale revealed that RU-486 and CP-99994 did not affect functional outcome, indicating that these pathways are dispensable for neuroprotection or repair after SCI. Moreover, the beta-blocker propranolol worsened functional outcome in the mouse SCI model. In conclusion, immediate inhibition of three major stress axes has no beneficial effects on functional recovery after SCI in mice. These results suggest that injury-induced stress responses do not interfere with the healing process and hence, pharmacological targeting of stress responses is not a recommended treatment option for SCI. These findings are of great importance for other researchers to avoid unnecessary and potentially futile animal experiments.
Notes: [Lemmens, Stefanie; Nelissen, Sofie; Geurts, Nathalie; Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Dept Morphol, Diepenbeek, Belgium. [Dooley, Dearbhaile] Univ Coll Dublin, Sch Med, Hlth Sci Ctr, Dublin, Ireland. [Peters, Eva Milena Johanne] Justus Liebig Univ, Psychoneuroimmunol Lab, Dept Psychosomat Med, Berlin, Germany. [Peters, Eva Milena Johanne] Charite, Berlin, Germany.
URI: http://hdl.handle.net/1942/29536
DOI: 10.1089/neu.2018.6211
ISI #: 000479852500001
ISSN: 0897-7151
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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