title: Acute leptin treatment enhances functional recovery after spinal cord injury.
abstract: BACKGROUND
  Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury.
  
  
  RESULTS
  Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning.
  
  
  CONCLUSIONS
  Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent.
authors.affiliation: Molecular Neurology Laboratory, Hospital Nacional de Parapléjicos (HNP), Toledo, Spain.
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Fernández-Martos
authors.forename: Pau
authors.initials: P
authors.lastname: González
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D020738:Leptin; D018696:Neuroprotective Agents; D047492:Peroxisome Proliferator-Activated Receptors; D054411:Receptors, Leptin