title: Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia.
abstract: BACKGROUND
  The acute phase protein pentraxin 3 (PTX3) is a new biomarker of stroke severity and is a key regulator of oedema resolution and glial responses after cerebral ischaemia, emerging as a possible target for brain repair after stroke. Neurogenesis and angiogenesis are essential events in post-stroke recovery. Here, we investigated for the first time the role of PTX3 in neurogenesis and angiogenesis after stroke.
  
  
  METHODS
  PTX3 knockout (KO) or wild-type (WT) mice were subjected to experimental cerebral ischaemia (induced by middle cerebral artery occlusion (MCAo)). Poststroke neurogenesis was assessed by nestin, doublecortin (DCX) and bromodeoxyuridine (BrdU) immunostaining, whereas angiogenesis was assessed by BrdU, vascular endothelial growth factor receptor 2 (VEGFR2) and PECAM-1 immunostaining. In vitro neurogenesis and angiogenesis assays were carried out on neurospheres derived from WT or interleukin-1β (IL-1β) KO mice, and mouse endothelial cell line bEnd.5 respectively. Behavioural function was assessed in WT and PTX3 KO mice using open-field, motor and Y-maze tests.
  
  
  RESULTS
  Neurogenesis was significantly reduced in the dentate gyrus (DG) of the hippocampus of PTX3 KO mice, compared to WT mice, 6 days after MCAo. In addition, recombinant PTX3 was neurogenic in vitro when added to neurospheres, which was mediated by IL-1β. In vivo poststroke angiogenesis was significantly reduced in PTX3 KO mice compared to WT mice 14 days after MCAo, as revealed by reduced vascular density, less newly formed blood vessels and decreased expression of VEGFR2. In vitro, recombinant PTX3 induced marked endothelial cellular proliferation and promoted formation of tube-like structures of endothelial cell line bEnd.5. Finally, a lack of PTX3 potentiated motor deficits 14 days after MCAo.
  
  
  CONCLUSIONS
  These results indicate that PTX3 mediates neurogenesis and angiogenesis and contributes to functional recovery after stroke, highlighting a key role of PTX3 as a mediator of brain repair and suggesting that PTX3 could be used as a new target for stroke therapy.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rodriguez-Grande
authors.forename: Lidiya
authors.initials: L
authors.lastname: Varghese
authors.forename: Francisco
authors.initials: F
authors.lastname: Molina-Holgado
authors.forename: Olivera
authors.initials: O
authors.lastname: Rajkovic
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Adam
authors.initials: A
authors.lastname: Denes
authors.affiliation: Faculty of Life Sciences, A,V, Hill Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. emmanuel.pinteaux@manchester.ac.uk.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000502:physiology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D020127:Recovery of Function; D020521:Stroke / Q000503:physiopathology*; D000099153:Pentraxins
chemical_list: D043925:Angiogenesis Inducing Agents; D002097:C-Reactive Protein; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D000099153:Pentraxins; C000714847:Dcx protein, mouse