System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish

PubMed: 40412555 DOI: 10.1016/j.peptides.2025.171415

Impact of galanin receptors 2 and 3 double-knockout on neuroinflammation and functional recovery following traumatic brain injury.

Peptides 191:171415

Authors: Susanne M Brunner, Stefanie Gaisbauer, Patrick N Pallier, Ping K Yip, Andrea Ramspacher, Julia Leitner, Felix Sternberg, Christina Erhardt-Kreutzer, Theresa Haslauer, Sara Huber, Lara Bieler, Sebastien Couillard-Despres, Barbara Kofler

Affiliations

  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Centre for Neuroscience, Surgery and Trauma, The Blizard Institute, Queen Mary University of London, United Kingdom.
  • Centre for Neuroscience, Surgery and Trauma, The Blizard Institute, Queen Mary University of London, United Kingdom.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria; Department of General, Visceral and Thoracic Surgery, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  • Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
  • Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
  • Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Abstract

Traumatic brain injury (TBI) is one of the world's leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL 1-3R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL 2R and GAL 3R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL 2/3R-double-KO (GAL 2/3R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1-28 post injury), neurological dysfunction was more severe in GAL 2/3R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL 2/3R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL 2R and/or GAL 3R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.

MeSH

Brain Injuries, Brain, Receptors, Galanin, Recycling, Brain Injuries, Traumatic, Galanin