Administration of TSG-6 improves memory after traumatic brain injury in mice

Neurobiol Dis. 2013 Nov;59:86-99. doi: 10.1016/j.nbd.2013.06.017. Epub 2013 Jul 11.


Traumatic brain injury (TBI) causes multiple long-term defects including a loss of working memory that is frequently incapacitating. Administrations of mesenchymal stem/stromal cells (MSCs) previously produced beneficial effects in models of TBI as well as other disease models. In several models, the beneficial effects were explained by the MSCs being activated to express TSG-6, a multifunctional protein that modulates inflammation. In a mouse model of TBI, we found the initial mild phase of the inflammatory response persisted for at least 24h and was followed by secondary severe response that peaked at 3days. Intravenous human MSCs or TSG-6 during initial mild phase decreased neutrophil extravasation, expression of matrix metalloproteinase 9 by endothelial cells and neutrophils, and the subsequent blood brain barrier leakage in secondary phase. Administration of TSG-6 also decreased the lesion size at 2weeks. Importantly, the acute administration of TSG-6 within 24h of TBI was followed 6 to 10weeks later by improvements in memory, depressive-like behavior and the number of newly born-neurons. The data suggested that acute administration of TSG-6 may be an effective therapy for decreasing some of the long-term consequences of TBI.

Keywords: BBB; Blood brain barrier; CCI; DCX; DG; FST; GCL; MMP; MPO; MSCs; Matrix metalloproteinase; Mesenchymal stem cells; NOR; NSFT; Neutrophils; SGZ; TBI; TLR; TSG-6; Traumatic brain injury; blood brain barrier; controlled cortical impact injury; dentate gyrus; doublecortin; forced swim test; granule cell layer; matrix metalloproteinase; mesenchymal stem cells; myeloperoxidase; novel object recognition; novelty suppressed feeding test; subgranular zone; toll-like receptor; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Injuries / complications*
  • Brain Injuries / therapy
  • Cell Adhesion Molecules / administration & dosage*
  • Cells, Cultured
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides / metabolism
  • Swimming / psychology
  • von Willebrand Factor / metabolism


  • Cell Adhesion Molecules
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • TNFAIP6 protein, human
  • Von Willebrand antigen
  • doublecortin protein
  • von Willebrand Factor
  • Matrix Metalloproteinase 9