PMID- 33314664 OWN - NLM STAT- MEDLINE DCOM- 20211207 LR - 20221129 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 27 IP - 1 DP - 2021 Jan TI - Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke. PG - 60-70 LID - 10.1111/cns.13510 [doi] AB - Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute-phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET-1 or L-Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP-positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood-brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel-based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte-derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof-of-concept that PTX3 could be a therapeutic target for white matter-related diseases, including stroke. CI - (c) 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. FAU - Shindo, Akihiro AU - Shindo A AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. AD - Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan. FAU - Takase, Hajime AU - Takase H AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Hamanaka, Gen AU - Hamanaka G AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Chung, Kelly K AU - Chung KK AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Mandeville, Emiri T AU - Mandeville ET AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Egawa, Naohiro AU - Egawa N AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. AD - Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Maki, Takakuni AU - Maki T AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. AD - Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Borlongan, Mia AU - Borlongan M AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Takahashi, Ryosuke AU - Takahashi R AD - Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Lok, Josephine AU - Lok J AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. AD - Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Tomimoto, Hidekazu AU - Tomimoto H AD - Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan. FAU - Lo, Eng H AU - Lo EH AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. FAU - Arai, Ken AU - Arai K AUID- ORCID: 0000-0003-1615-3258 AD - Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. LA - eng GR - R01 NS065089/NS/NINDS NIH HHS/United States GR - R01 NS091573/NS/NINDS NIH HHS/United States GR - R01 NS113556/NS/NINDS NIH HHS/United States GR - R21 AG066478/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20201211 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (neuronal pentraxin) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Aged MH - Aged, 80 and over MH - Animals MH - Blood-Brain Barrier/drug effects/*metabolism MH - C-Reactive Protein/administration & dosage/antagonists & inhibitors/*biosynthesis MH - Cells, Cultured MH - Female MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/administration & dosage/antagonists & inhibitors/*biosynthesis MH - RNA, Small Interfering/administration & dosage MH - Rats MH - Recovery of Function/drug effects/*physiology MH - Stroke/*drug therapy/*metabolism/pathology MH - White Matter/drug effects/*metabolism/pathology PMC - PMC7804900 OTO - NOTNLM OT - angiogenesis OT - blood-brain barrier OT - neurovascular unit OT - pentraxin 3 OT - stroke OT - white matter COIS- None. EDAT- 2020/12/15 06:00 MHDA- 2021/12/15 06:00 PMCR- 2020/12/11 CRDT- 2020/12/14 11:16 PHST- 2020/08/30 00:00 [received] PHST- 2020/10/24 00:00 [revised] PHST- 2020/10/25 00:00 [accepted] PHST- 2020/12/15 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2020/12/14 11:16 [entrez] PHST- 2020/12/11 00:00 [pmc-release] AID - CNS13510 [pii] AID - 10.1111/cns.13510 [doi] PST - ppublish SO - CNS Neurosci Ther. 2021 Jan;27(1):60-70. doi: 10.1111/cns.13510. Epub 2020 Dec 11.