Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia.

Beatriz Rodriguez-Grande, Lidiya Varghese, Francisco Molina-Holgado, Olivera Rajkovic, Cecilia Garlanda, Adam Denes, Emmanuel Pinteaux
Journal of Neuroinflammation. 2015-01-01; 12(1): 15
DOI: 10.1186/s12974-014-0227-y

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1. J Neuroinflammation. 2015 Jan 24;12:15. doi: 10.1186/s12974-014-0227-y.

Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia.

Rodriguez-Grande B, Varghese L, Molina-Holgado F, Rajkovic O, Garlanda C, Denes
A, Pinteaux E(1).

Author information:
(1)Faculty of Life Sciences, A,V, Hill Building, University of Manchester, Oxford
Road, Manchester M13 9PT, UK. .

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
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.

DOI: 10.1186/s12974-014-0227-y
PMCID: PMC4308938
PMID: 25616391 [Indexed for MEDLINE]

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