Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke

Ivana Rajkovic, Raymond Wong, Eloise Lemarchand, Jack Rivers-Auty, Olivera Rajkovic, Cecilia Garlanda, Stuart M Allan, Emmanuel Pinteaux

Research output: Contribution to journalArticle

Abstract

Restoration of cerebral blood flow (CBF) and upregulation of angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Here, we investigated for the first time the role of PTX3 in long-term CBF, angiogenesis, and neuronal viability after ischaemic stroke induced by transient middle cerebral artery occlusion (MCAo). Lack of PTX3 had no effect on early brain damage, but significantly impaired restoration of CBF, 14 and 28 days after MCAo, compared to wild-type (WT) mice. Immunohistochemical analysis revealed that PTX3 KO mice have significantly greater neuronal loss, significantly decreased vessel diameter, vessel proliferation, vascular density, and reactive astrocytes and decreased expression of vascular endothelial growth factor receptor 2 (VEGR2), vascular extracellular matrix (ECM)-proteins (collagen IV, laminin), and integrin-β, in the ipsilateral (stroke) hemisphere compared to WT mice, 28 days after MCAo. Therefore, PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia. Collectively, these findings demonstrate the potential and clinical relevance of PTX3 as a promising therapeutic target, providing sustained long-term post-stroke neurovascular repair and reducing the loss of neurons. KEY MESSAGES: Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Restoration of cerebral blood flow (CBF) and angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia.

Original languageEnglish
Pages (from-to)1319-1332
Number of pages14
JournalJournal of Molecular Medicine
Volume96
Issue number12
DOIs
Publication statusPublished - Dec 2018

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Cerebrovascular Circulation
Stroke
Brain Ischemia
Middle Cerebral Artery Infarction
Blood Vessels
Brain
Vascular Endothelial Growth Factor Receptor-2
PTX3 protein
Extracellular Matrix Proteins
Laminin
Integrins
Astrocytes
Up-Regulation
Collagen

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Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke. / Rajkovic, Ivana; Wong, Raymond; Lemarchand, Eloise; Rivers-Auty, Jack; Rajkovic, Olivera; Garlanda, Cecilia; Allan, Stuart M; Pinteaux, Emmanuel.

In: Journal of Molecular Medicine, Vol. 96, No. 12, 12.2018, p. 1319-1332.

Research output: Contribution to journalArticle

Rajkovic, I, Wong, R, Lemarchand, E, Rivers-Auty, J, Rajkovic, O, Garlanda, C, Allan, SM & Pinteaux, E 2018, 'Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke' Journal of Molecular Medicine, vol. 96, no. 12, pp. 1319-1332. https://doi.org/10.1007/s00109-018-1698-6
Rajkovic, Ivana ; Wong, Raymond ; Lemarchand, Eloise ; Rivers-Auty, Jack ; Rajkovic, Olivera ; Garlanda, Cecilia ; Allan, Stuart M ; Pinteaux, Emmanuel. / Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke. In: Journal of Molecular Medicine. 2018 ; Vol. 96, No. 12. pp. 1319-1332.
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AU - Garlanda, Cecilia

AU - Allan, Stuart M

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AB - Restoration of cerebral blood flow (CBF) and upregulation of angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Here, we investigated for the first time the role of PTX3 in long-term CBF, angiogenesis, and neuronal viability after ischaemic stroke induced by transient middle cerebral artery occlusion (MCAo). Lack of PTX3 had no effect on early brain damage, but significantly impaired restoration of CBF, 14 and 28 days after MCAo, compared to wild-type (WT) mice. Immunohistochemical analysis revealed that PTX3 KO mice have significantly greater neuronal loss, significantly decreased vessel diameter, vessel proliferation, vascular density, and reactive astrocytes and decreased expression of vascular endothelial growth factor receptor 2 (VEGR2), vascular extracellular matrix (ECM)-proteins (collagen IV, laminin), and integrin-β, in the ipsilateral (stroke) hemisphere compared to WT mice, 28 days after MCAo. Therefore, PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia. Collectively, these findings demonstrate the potential and clinical relevance of PTX3 as a promising therapeutic target, providing sustained long-term post-stroke neurovascular repair and reducing the loss of neurons. KEY MESSAGES: Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Restoration of cerebral blood flow (CBF) and angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia.

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